Official OSA COVID-19/Corona Virus Thread

[_CY_]

British Medical Journal speaks of CRIMINALIZING QUESTIONING VACCINE SAFETY!!! (youtu.be)

Editorials
Developing a vaccine for covid-19
BMJ 2020; 369 doi: https://doi.org/10.1136/bmj.m1790 (Published 04 May 2020)Cite this as: BMJ 2020;369:m1790
Read our latest coverage of the coronavirus pandemic

• Article
• Related content
• Metrics
• Responses

1. Sarah Caddy, Wellcome Trust clinical research career development fellow

1. 
   Author affiliations

1. [email protected]

Old and new strategies are being investigated in an unprecedented worldwide effort

The rapidly developing covid-19 epidemic has stimulated an enormous effort to develop vaccines against the coronavirus SARS-CoV-2. At least six vaccine candidates have entered clinical trials across the globe, with more than 80 other candidates reported to be in preclinical stages.1 This means many different approaches are being moved forward at the same time. However, the road to successful vaccine licensure is treacherous, and only a handful of these vaccines may make it.

No vaccines are currently licensed for any of the other coronaviruses affecting humans—SARS-CoV-1, MERS-CoV, and minor cold viruses. Economic reasons are undoubtedly a major factor for the absence of these vaccines, but vaccine design is also a challenge; immune responses to natural coronavirus infections can be short lived, and some trial vaccines for SARS-CoV-1 raised safety concerns in animal models.2 The development of a SARS-CoV-2 vaccine therefore may not be straightforward.

The multiple strategies to vaccine development for covid-19 include both traditional methods and next generation techniques. Historically, vaccines comprised inactivated whole virus, attenuated virus (less virulent but still immunogenic), or parts or subunits of the virus. Live vaccines are not likely to be attempted for covid-19 for safety reasons, but an inactivated whole virus vaccine has been taken through to preclinical trials in primates.3 When challenged with SARS-CoV-2, vaccinated macaques were protected from severe disease and cleared the virus within a week, whereas macaques receiving placebo developed severe interstitial pneumonia. A phase I-II human trial of this inactivated vaccine is now underway in China.4

Spike protein
Many other efforts are currently focused on the spike protein in SARS-CoV-2. This protein is part of the outer layer of the virus and is critical for entry into cells. Antibodies that target the spike protein can block virus entry, potentially inhibiting subsequent virus replication.5 The genetic sequence of the spike protein was released internationally on 10 January 2020, providing a blueprint for vaccine development.67

Widely reported UK contributions towards a SARS-CoV-2 vaccine are based on the spike protein. Scientists at the University of Oxford have modified a chimp adenovirus vector to carry the spike protein gene. When the adenovirus invades human cells, the spike protein will be produced, becoming a potential target for an immune response. The clinical trial for this vaccine started on 23 April and plans to recruit over 1000 volunteers.8

The use of messenger RNA as a vaccine is a relatively new strategy, and no licenced vaccines have yet used this method. The concept is simple though—inject mRNA coding for the spike protein and let the host make the protein. One advantage of this approach is a reasonably straightforward route to manufacture, allowing rapid scaling up of production. The first mRNA vaccine entered clinical trials in the US six weeks ago, and preliminary results are eagerly awaited. Related work is ongoing at Imperial College London, with promising results in mice released at the end of April.9

Other vaccine strategies under consideration include injecting DNA coding for the spike protein or the actual spike protein (“recombinant protein”). Others are using just the tip domain of the spike protein as this is the part that targets the receptors on human cells. Examples of these approaches are likely to enter phase I clinical trials this year.

Repurposing other vaccines
Repurposing vaccines to treat covid-19 is being considered as an alternative means of virus control. Hundreds of vaccines are licensed worldwide for non-coronavirus pathogens, and associations have been made between general vaccine uptake in a country and covid-19 severity.

The current frontrunner is the BCG vaccine, normally directed against tuberculosis. BCG vaccine can stimulate broad, innate components of the immune system, offering some protection against a range of diseases from influenza to bladder cancer.1011 Several studies have now proposed an epidemiological link between population BCG coverage and reduced covid-19 incidence at a country level.1213 Although several rebuttal studies have also been published, at least five clinical trials are now recruiting healthcare workers to investigate whether BCG protects them against covid-19.14

Other potential repurposed vaccines include the oral polio vaccine15 and the MMR vaccine.16 All these existing vaccines have the advantage that they can begin phase III trials immediately as safety (phase I) and immunogenicity (phase II) have already been established. However, evidence for their use must be regarded as tenuous at this point.

Which vaccine will make it successfully through clinical trials first? It’s too early to tell, and in an ideal world we would have several safe and effective vaccines. No single vaccine will be suitable for everyone, everywhere. Access will be particularly challenging for low income countries, where financial support will be essential.

Having choice will also increase the scale of overall production, using a variety of manufacturing options. While fast tracking research and development is an option in all well resourced countries, the most realistic time frame for the production at scale of any safe and effective vaccine against covid-19 still stands at over a year.

Acknowledgments
I thank Gordon Dougan for constructive comments.

Footnotes

• Competing interests: The BMJ has judged that there are no disqualifying financial ties to commercial companies. The authors declare no interests. The BMJ policy on financial interests is here: www.bmj.com/sites/default/files/attachments/resources/2016/03/16-current-bmj-education-coi-form.pdf.
  
  
• Provenance and peer review: Commissioned; not externally peer reviewed.

References

1. ↵
   Milken Institute. COVID-19 treatment and vaccine tracker. 2020. https://milkeninstitute.org/sites/default/files/2020-04/Covid19TrackerNEW4-21-20-2.pdf
   
   
2. ↵
   1. Amanat F,
   2. Krammer F
   . SARS-CoV-2 vaccines: status report. Immunity2020;52:583-9.doi:10.1016/j.immuni.2020.03.007 pmid:32259480
   CrossRefPubMedGoogle Scholar
3. ↵
   Gao AQ, Bao L, Mao H, et al. Rapid development of an inactivated vaccine for SARS-CoV-2. bioRxiv 2020.04.17.046375. [Preprint.] 2020. doi:10.1101/2020.04.17.046375.
   Abstract/FREE Full TextGoogle Scholar
4. ↵
   Safety and immunogenicity study of inactivated vaccine for prophylaxis of SARS CoV-2 infection (covid-19). Trial No NCT04352608. https://clinicaltrials.gov/ct2/show/NCT04352608.
   
   
5. ↵
   1. Walls AC,
   2. Park YJ,
   3. Tortorici MA,
   4. et al
   . Structure, function, and antigenicity of the SARS-CoV-2 spike glycoprotein. Cell2020;181:281-292.e6. doi:10.1016/j.cell.2020.02.058 pmid:32155444
   CrossRefPubMedGoogle Scholar
6. ↵
   1. Zhou P,
   2. Yang X-L,
   3. Wang X-G,
   4. et al
   . A pneumonia outbreak associated with a new coronavirus of probable bat origin. Nature2020;579:270-3. doi:10.1038/s41586-020-2012-7 pmid:32015507
   CrossRefPubMedGoogle Scholar
7. ↵
   1. Zhu N,
   2. Zhang D,
   3. Wang W,
   4. et al.,
   5. China Novel Coronavirus Investigating and Research Team
   . A novel coronavirus from patients with pneumonia in China, 2019. N Engl J Med2020;382:727-33. doi:10.1056/NEJMoa2001017 pmid:31978945
   CrossRefPubMedGoogle Scholar
8. ↵
   Oxford University. A study of a candidate COVID-19 vaccine (COV001). Trial No NCT04324606. https://www.clinicaltrials.gov/ct2/show/NCT04324606
   
   
9. ↵
   Mckay PF, Hu K, Blakney AK, et al. Self-amplifying RNA SARS-CoV-2 lipid nanoparticle vaccine induces equivalent preclinical antibody titers and viral neutralization to recovered COVID-19 patients. bioRxiv 2020.04.22.055608 [Preprint.] 2020.doi:10.1101/2020.04.22.055608
   Abstract/FREE Full TextGoogle Scholar
10. ↵
    1. Moorlag SJCFM,
    2. Arts RJW,
    3. van Crevel R,
    4. Netea MG
    . Non-specific effects of BCG vaccine on viral infections. Clin Microbiol Infect2019;25:1473-8. doi:10.1016/j.cmi.2019.04.020 pmid:31055165
    CrossRefPubMedGoogle Scholar
11. ↵
    1. Guallar-Garrido S,
    2. Julián E
    . Bacillus Calmette-Guérin (BCG) therapy for bladder cancer: an update. Immunotargets Ther2020;9:1-11. doi:10.2147/ITT.S202006 pmid:32104666
    CrossRefPubMedGoogle Scholar
12. ↵
    Miller A, Reandelar MJ, Fasciglione K, et al. Correlation between universal BCG vaccination policy and reduced morbidity and mortality for COVID-19: an epidemiological study. MedRxiv 2020.03.24.20042937 [Preprint.] doi:10.1101/2020.03.24.20042937.
    Abstract/FREE Full TextGoogle Scholar
13. ↵
    Dayal D, Gupta S. Connecting BCG vaccination and COVID-19: additional data. MedRxiv 2020.04.07.20053272. [Preprint.] 2020, doi:10.1101/2020.04.07.20053272
    Abstract/FREE Full TextGoogle Scholar
14. ↵
    1. US National Library of Medicine
    . https://www.clinicaltrials.gov/ct2/results?cond=COVID-19+&term=vaccine
    Google Scholar
15. ↵
    Chumakov K, Gallo R. Could an old vaccine be a godsend for new coronavirus? 2020.https://eu.usatoday.com/story/opini...otential-treat-coronavirus-column/5162859002/
    
    
16. ↵
    Young A, Neumann B, Mendez RF, et al. Homologous protein domains in SARS-CoV-2 and measles, mumps and rubella viruses: preliminary evidence that MMR vaccine might provide protection against COVID-19. MedRxiv 2020.04.10.20053207. [Preprint.] 2020. doi:10.1101/2020.04.10.20053207
    Abstract/FREE Full Text

your ignorance is showing .. ha ha ha
do you even bother reading before you post?

article says NOTHING about alleged safety of mRNA "vaccines" aka gene therapy that NO one in the world knows what long term side effects will be.

NO mRNA "vaccine" has passed phase 3 safety trials. simply not possible for a experimental drug only 9 months old. big pharma are NOT responsible for damages from side effects in America, then factor in US gov is NOT responsible damages from experimental "vaccines".

one very important factor that probably beyond your comprehension level. currently NO one in the world has access to a complete SARS COV-2 genome, only snippets. if NO one can get access to a complete genome, then how in the world can anyone measure how effective said mRNA "vaccine" gene therapy is?

 

[_CY_]

https://covid19criticalcare.com/

I'm gonna leave this here. I'm not gonna debate anything with you guys. This is here for your information. It's up to you whether you read it or not. Believe it or not. Use it or not. Enjoy.

excellent post! documenting effectiveness of ivermectin/zinc/doxycycline ... shutting down C-19 at generic costs with an almost 100% response rate for improvement .. very safe.

best of all ivermectin still works down to about 50% O2 levels.

why in the world would anyone want to invoke unknown risks of experimental mRNA "vaccines" ? when C-19 is so easily treatable with ivermectin?

C-19 has a survival rate of 99.5%+ for folks under age 70 with no treatment. I'd rather get C-19, then take ivermectin/zinc/doxycycline to knock it out vs experimental mRNA "vaccine"

some doctors are claiming one dose of imvermectin shuts down spread of C-19 for about 3 months.

everyone should read this ..

 

[_CY_]

The Moderna COVID-19 (mRNA-1273) vaccine: what you need to know
https://www.who.int/

Does it prevent infection and transmission?
We do not know whether the vaccine will prevent infection and protect against onward transmission. Immunity persists for several months, but the full duration is not yet known. These important questions are being studied.

In the meantime, we must maintain public health measures that work: masking, physical distancing, handwashing, respiratory and cough hygiene, avoiding crowds, and ensuring good ventilation.

Is it safe?
While this vaccine has yet to be approved by WHO for an Emergency Use Listing

Those who experience an immediate severe allergic reaction to the first dose should not receive additional doses.

Longer-term safety assessment involves continued follow up of clinical trial participants, as well as specific studies and continued surveillance of secondary effects or adverse events of those being vaccinated in the roll out.

• Comment
• Published: 23 July 2020

Next-generation vaccine platforms for COVID-19

• Nature Materials volume 19, pages810–812(2020)Cite this article
  • 57k Accesses
    
    
  • 20 Citations
    
    
  • 154 Altmetric
    
    
  • Metrics details

Consensus among experts is that only an effective COVID-19 vaccine will end the pandemic. This Comment focuses on how this pandemic has accelerated the development of vaccine platforms distinct from classical vaccines; these novel platforms may also increase the response time when new viruses emerge in the future.

An outbreak of highly pathogenic avian influenza (HPAI) virus of the H5N1 subtype was diagnosed in Hong Kong in 1997, with 18 human cases including six deaths. This was the first known outbreak of influenza A virus resulting from direct transmission of an avian influenza virus from chickens to humans without an intermediate reservoir such as pigs1. This outbreak increased the awareness of the risk of a devastating pandemic, and showed that more resources should be diverted to pandemic preparedness planning2. Many considered this an overblown response to a small outbreak, aimed at acquiring more research funding, especially when years went by without an H5N1 pandemic, despite the widespread, continued circulation of HPAI H5N1 in poultry with regular spillover to humans, resulting in more than 850 human cases and over 450 deaths to date3. The emergence of severe acute respiratory syndrome coronavirus (SARS-CoV) in 2002 put everyone on alert for a while, but this pandemic was contained through old-fashioned contact tracing and isolation procedures after causing >8,000 cases in 27 countries4. Subsequently, the 2009 H1N1 pandemic turned out to be relatively mild, with a low case fatality rate5. The Ebola virus epidemic in West Africa in 2013–2016 was a turning point. Whereas the largest previous Ebola virus outbreaks had resulted in several hundred cases in confined areas, this epidemic resulted in close to 30,000 cases in ten countries and took more than three years to bring under control6. The unprecedented number of cases, geographic spread, and enormous amount of money and effort needed to end this epidemic made clear that zoonotic viruses pose an immense threat to global health and economies. Efforts were launched to identify viruses with epidemic potential7, and money was invested in developing vaccines against some of these, as well as in the development of new, rapid vaccine platforms. Now, six months after the discovery of SARS-CoV-2, antivirals and vaccines are in development, with many treatment options and vaccines in clinical trials worldwide. Even though antivirals are important to dampen the disease burden of the current pandemic, effective vaccines are essential to control it. The World Health Organization (WHO) estimates that there are 133 COVID-19 vaccines in development8. Many of these are novel platforms with little pre-existing data on safety and efficacy in humans.

Classic vaccine platforms
The vast majority of vaccines currently licensed for human use can be divided into virus-based or protein-based vaccines (Fig. 1). The virus-based vaccines can consist of inactivated virus that is no longer infectious, or live-attenuated virus. Since whole-inactivated viruses do not replicate, adjuvants are required to stimulate the immune system. Live-attenuated virus vaccines are classically generated by passaging in cell culture until it loses its pathogenic properties and causes only a mild infection upon injection. Protein-based vaccines can consist of a protein purified from the virus or virus-infected cells, recombinant protein or virus-like particles. Virus-like particles consist of the structural viral proteins necessary to form a virus particle, but lack the viral genome and non-structural proteins. Protein-based vaccines require the addition of an adjuvant to induce a strong immune response. Two COVID-19 vaccines based on these classical platforms are currently in clinical trials, one based on whole-inactivated virus and one consisting of recombinant protein (Fig. 1).

Fig. 1: An overview of the different vaccine platforms in development against COVID-19.

A schematic representation is shown of the classical vaccine platforms that are commonly used for human vaccines, and next-generation platforms, where very few have been licensed for use in humans. The stage of development for each of these vaccine platforms for COVID-19 vaccine development is shown; online vaccine trackers are available to follow these vaccines through the clinical development and licensing process21.

Full size image
These classical vaccine platforms have contributed to major public health breakthroughs, such as the eradication of smallpox and a vaccine to prevent cancer9,10. However, certain limitations are associated with several of these platforms that make them less amenable to fast vaccine production in a pandemic. In the case of SARS-CoV-2, large quantities of virus would need to be grown under biosafety level 3 (BSL3) conditions for a whole-inactivated vaccine; extensive safety testing is required to ensure live-attenuated viruses are safe and do not easily revert to wild type, and several recombinant proteins need to be produced simultaneously for virus-like particle vaccines.

Next-generation vaccine platforms
The main advantage of next-generation vaccines is that they can be developed based on sequence information alone. If the viral protein(s) important to provide protection from infection or disease, and thus for inclusion in a vaccine (that is, the vaccine antigen), is known the availability of coding sequences for this viral protein(s) suffices to start vaccine development, rather than having to depend on the ability to culture the virus. This makes these platforms highly adaptable and speeds up vaccine development considerably, as is clear from the fact that the majority of COVID-19 vaccine clinical trials currently ongoing involve a next-generation platform (Fig. 1).

For COVID-19, several viral vector, nucleic acid-based vaccines and antigen-presenting cells are in (pre)clinical development (Fig. 1). Viral vector vaccines consist of a recombinant virus (that is, the viral vector), often attenuated to reduce its pathogenicity, in which genes encoding viral antigen(s) have been cloned using recombinant DNA techniques. Vector vaccines can either be replicating or non-replicating. Replicating vector vaccines infect cells in which the vaccine antigen is produced as well as more infectious viral vectors able to infect new cells that will then also produce the vaccine antigen. Non-replicating vector vaccines initially enter cells and produce the vaccine antigen, but no new virus particles are formed. Because viral vector vaccines result in endogenous antigen production, both humoral and cellular immune responses are stimulated. One advantage of these viral vector-based vaccines is therefore that a single dose can be sufficient for protection, as in the case of the vesicular-stomatitis virus-based Ervebo vaccine against Ebola virus11.

Nucleic acid-based vaccines can consist of DNA or mRNA and can be adapted quickly when new viruses emerge, which is why these were among the very first COVID-19 vaccines to enter clinical trials. DNA vaccines consist of a synthetic DNA construct encoding the vaccine antigen. For efficient uptake of the construct into cells, injection needs to be followed by electroporation. After uptake into cells, the vaccine antigen is expressed from the DNA construct. mRNA-based vaccines work on the same principle as DNA vaccines, except that the first steps (nuclear translocation of the DNA construct and transcription into mRNA) are bypassed. Self-replicating RNA vaccines are likely to induce protective immunity using a lower dose, because more vaccine antigen is expressed per cell12. Since mRNA is not very stable, these constructs include modified nucleosides to prevent degradation. A carrier molecule is necessary to enable entry of the mRNA into cells; lipid nanoparticles are most commonly used. Nucleic acid-based vaccines induce a humoral and cellular immune response, but multiple doses are required.

Antigen-presenting cells are an essential component in the immune system’s response to a vaccine. Loading antigen-presenting cells with peptides that would otherwise be produced by vaccination bypasses the first steps after vaccination. Traditionally, dendritic cells are harvested from the individual, then expanded and manipulated to present the desired antigen, and infused back into the same individual. This is cost-prohibitive and too time-consuming for a vaccine deployed on a large scale. This has led to the development of artificial antigen-presenting cells, where immortalized cells are transduced with lentiviruses to effectively mimic antigen-presenting cells, as is the case for COVID-19/aAPC. Extra cold-chain requirements for a cell-based vaccine and infusion procedures hamper the deployment of these vaccines on a large scale, even more so since multiple doses are required for an efficient response. COVID-19 vaccines based on all next-generation platforms are currently in clinical trials; some of these have already moved from phase 1 into phase 2 or 2/3 (Fig. 1).

Vaccine requirements and challenges
While the development of vaccines against COVID-19 is ongoing, it is important to define what we expect from this vaccine, or vaccines for future emerging viruses. Needless to say, the vaccine should be safe and effective, and should not induce enhanced disease upon subsequent infection, whether through vaccine-associated enhanced respiratory disease or antibody-dependent enhancement, as has been observed with certain SARS-CoV vaccines in animal models in the past13. In order to prevent severe disease after infection, vaccination should result in either (1) complete abrogation or significant reduction of transmission within the population by the induction of herd immunity or (2) prevention of severe disease in all vaccinated individuals. Both approaches would require the production of large quantities of vaccine, distributed worldwide. A single dose vaccine that would not require a cold chain would contribute to the timeframe in which large-scale, global vaccination can be achieved. Ideally, vaccination would induce long-lived immunity, but annual vaccination would be feasible based on experiences with the annual influenza vaccine. Vaccination campaigns that either induce herd immunity or protect vaccinated individuals from severe disease face different challenges. Herd immunity for SARS-CoV-2 would require vaccination of ~67% of the population14, which is an average and would not prevent clusters of susceptible individuals. However, in recent years vaccine hesitance, identified as a major threat to global health by the WHO15, increased in many countries, and a recent study showed that 26% of the French population would not take a SARS-CoV-2 vaccine16. Vaccination that does not abrogate transmission but does result in protection from severe disease seems more straightforward. However, two important risk groups for developing severe COVID-19, elderly (>65 years old) and obesity (body mass index > 40) have previously been linked to reduced vaccine efficacy using classical vaccination approaches17,18. Whether new vaccine platforms have an increased immunogenicity in these risk groups compared to classical vaccination approaches remains to be determined.

Besides the question of efficacy for any of the COVID-19 vaccines under development, a major hurdle will be large-scale manufacturing. Since the next-generation platforms, with the exception of two viral vector-based vaccines (Dengvaxia and Ervebo) are not licensed for use in humans, the feasibility to rapidly manufacture these on a large-scale is currently unclear19. Although vaccine manufacturing capacity exists for the classical platforms, using the existing infrastructure would potentially go at the expense of regular vaccine production. Maintaining vaccination status for all vaccine-preventable diseases, while at the same time producing hundreds of millions of doses of COVID-19 vaccines, will be essential for global health. Besides the vaccine antigen itself, the required adjuvants or delivery molecules and, in the case of DNA vaccines, special delivery devices, will need to be manufactured on a mass scale as well. To be of use, hundreds of millions of doses need to be manufactured and distributed. Moreover, with the potential exception of DNA vaccines, all vaccines require a cold chain for distribution. Therefore, many international initiatives and investments are currently made to increase the capacity to produce and distribute vaccines. These collaborative programmes will be crucial for the large-scale deployment of vaccines to contain the COVID-19 pandemic; global distribution to prevent disparities in vaccination programmes between high-income countries and the rest of the world is essential in this effort.

Future directions
The development of many of the next-generation platforms described here has so far been driven mainly by their potential use in cancer therapies. The COVID-19 pandemic has fast-tracked their development as vaccine platforms for emerging viruses. If current predictions become reality, the first vaccines against COVID-19 will be licensed within a year. These licensed vaccines are likely to include some of the next-generation platforms described here. This in itself will be a major public health achievement, yet will simultaneously result in a permanent change to the vaccine platform landscape and an increased vaccine manufacturing capacity for these novel platforms. Plans should be developed to ensure that the large-scale manufacturing infrastructure being built now to respond to the COVID-19 pandemic is maintained for potential future vaccine needs, as has been done for influenza vaccines20.

Once next-generation platforms are licensed, their use for other pathogens or disease indications are likely to become more easily attainable. Since these platforms only require sequence information to initiate vaccine development, this will increase the flexibility to adapt vaccines to antigenic changes in circulating strains, and to newly emerging viruses in general. The wider array of possibilities for pre-emptive and reactive vaccine design, as well as faster development and manufacturing options, will permanently change our ability to rapidly respond to emerging viruses. As such, the investments made now in vaccine platform development and manufacturing will pay off when we are able to respond even faster when a new virus emerges in the future.

References

1. 1.
   Chan, P. K. S. Clin. Infect. Dis. 34, S58–S64 (2002).
   
   Article Google Scholar
   
   
2. 2.
   Iskander, J., Strikas, R. A., Gensheimer, K. F., Cox, N. J. & Redd, S. C. Emerg. Infect. Dis. 19, 879–885 (2013).
   
   Article Google Scholar
   
   
3. 3.
   Cumulative Number of Confirmed Human Cases for Avian Influenza A(H5N1) Reported to WHO, 2003–2020 (WHO, 2020); https://www.who.int/influenza/human_animal_interface/2020_MAY_tableH5N1.pdf?ua=1
   
   
4. 4.
   Summary of Probable SARS Cases with Onset of Illness from 1 November 2002 to 31 July 2003 (WHO, 2003); https://www.who.int/csr/sars/country/table2004_04_21/en/
   
   
5. 5.
   Wong, J. Y. et al. Epidemiology 24, 830–841 (2013).
   
   Article Google Scholar
   
   
6. 6.
   Bausch, D. G. Curr. Top. Microbiol. Immunol. 411, 63–92 (2017).
   
   Google Scholar
   
   
7. 7.
   Mehand, M. S., Al-Shorbaji, F., Millett, P. & Murgue, B. Antiviral Res. 159, 63–67 (2018).
   
   CAS Article Google Scholar
   
   
8. 8.
   DRAFT Landscape of COVID-19 Candidate Vaccines (WHO, 2020); https://www.who.int/who-documents-detail/draft-landscape-of-covid-19-candidate-vaccines
   
   
9. 9.
   Greenwood, B. Philos. Trans. R. Soc. Lond. B 369, 20130433 (2014).
   
   Article Google Scholar
   
   
10. 10.
    Patel, C. et al. Euro. Surveill. 23, 30–40 (2018).
    
    Article Google Scholar
    
    
11. 11.
    Henao-Restrepo, A. M. et al. Lancet 389, 505–518 (2017).
    
    CAS Article Google Scholar
    
    
12. 12.
    Vogel, A. B. et al. Mol. Ther. 26, 446–455 (2018).
    
    CAS Article Google Scholar
    
    
13. 13.
    Graham, B. S. Science 368, 945–946 (2020).
    
    CAS Article Google Scholar
    
    
14. 14.
    Randolph, H. E. & Barreiro, L. B. Immunity 52, 737–741 (2020).
    
    CAS Article Google Scholar
    
    
15. 15.
    Ten Threats to Global Health in 2019 (WHO, 2019); https://www.who.int/news-room/feature-stories/ten-threats-to-global-health-in-2019
    
    
16. 16.
    Coconel Group Lancet Infect. Dis. 20, 769–770 (2020).
    
    
17. 17.
    Ciabattini, A. et al. Semin. Immunol. 40, 83–94 (2018).
    
    Article Google Scholar
    
    
18. 18.
    Sheridan, P. A. et al. Int. J. Obes. 36, 1072–1077 (2012).
    
    CAS Article Google Scholar
    
    
19. 19.
    Thanh Le, T. et al. Nat. Rev. Drug Discov. 19, 305–306 (2020).
    
    Article Google Scholar
    
    
20. 20.
    McLean, K. A., Goldin, S., Nannei, C., Sparrow, E. & Torelli, G. Vaccine 34, 5410–5413 (2016).
    
    Article Google Scholar
    
    
21. 21.
    Craven, J. COVID-19 Vaccine Tracker (RAPS, 2020); https://www.raps.org/news-and-articles/news-articles/2020/3/covid-19-vaccine-tracker

Download references

Acknowledgements
The authors would like to thank V. Munster (National Institute of Allergy and Infectious Diseases, National Institutes of Health) for critically reading the manuscript and R. Kissinger (National Institute of Allergy and Infectious Diseases, National Institutes of Health) for preparing the figure. D.v.R. is supported by the Netherlands Organization for Scientific Research (grant number 91718308) and a EUR fellowship. E.d.W. is supported by the Intramural Research Program of National Institute of Allergy and Infectious Diseases, National Institutes of Health.

more of your ignorance showing ... ha ha ha
do you even bother reading before you post?
a better question is ... do you even understand the topic?
based on your two responses .. you really don't understand.

your article flat doesn't cover the two questions brought up.

Does it prevent infection and transmission?

Is it safe?

 

[ConstitutionCowboy]

Do y'all remember some time back when Bill Blowjob was president and there was some sort of push for single payer health care and Hilary was deeply involved and there was some sort of flap over involvement of drug companies etc., etc.? Maybe this Covid-19 BS is the culmination - the payoff - the coup-d-gra (Spelling?) - the end of life as we know it - a THX1138 civilization instituted - - -

Don't tell me about how too many people would have to be in on the scam to make it work. Look at Hitler.

Woody

 

[JD8]

British Medical Journal speaks of CRIMINALIZING QUESTIONING VACCINE SAFETY!!! (youtu.be)





your ignorance is showing .. ha ha ha
do you even bother reading before you post?

article says NOTHING about alleged safety of mRNA "vaccines" aka gene therapy that NO one in the world knows what long term side effects will be.

NO mRNA "vaccine" has passed phase 3 safety trials. simply not possible for a experimental drug only 9 months old. big pharma are NOT responsible for damages from side effects in America, then factor in US gov is NOT responsible damages from experimental "vaccines".

one very important factor that probably beyond your comprehension level. currently NO one in the world has access to a complete SARS COV-2 genome, only snippets. if NO one can get access to a complete genome, then how in the world can anyone measure how effective said mRNA "vaccine" gene therapy is?

Given your postings, I don't think you could make it through a 9th grade microbiology course.

I get it that all you know is what you search on the internet but damn son......you just dig yourself deeper in the hole with every post.


https://www.nejm.org/doi/full/10.1056/NEJMoa2035389


Abstract
BACKGROUND
Vaccines are needed to prevent coronavirus disease 2019 (Covid-19) and to protect persons who are at high risk for complications. The mRNA-1273 vaccine is a lipid nanoparticle–encapsulated mRNA-based vaccine that encodes the prefusion stabilized full-length spike protein of the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), the virus that causes Covid-19.

METHODS
This phase 3 randomized, observer-blinded, placebo-controlled trial was conducted at 99 centers across the United States. Persons at high risk for SARS-CoV-2 infection or its complications were randomly assigned in a 1:1 ratio to receive two intramuscular injections of mRNA-1273 (100 μg) or placebo 28 days apart. The primary end point was prevention of Covid-19 illness with onset at least 14 days after the second injection in participants who had not previously been infected with SARS-CoV-2.

RESULTS

The trial enrolled 30,420 volunteers who were randomly assigned in a 1:1 ratio to receive either vaccine or placebo (15,210 participants in each group). More than 96% of participants received both injections, and 2.2% had evidence (serologic, virologic, or both) of SARS-CoV-2 infection at baseline. Symptomatic Covid-19 illness was confirmed in 185 participants in the placebo group (56.5 per 1000 person-years; 95% confidence interval [CI], 48.7 to 65.3) and in 11 participants in the mRNA-1273 group (3.3 per 1000 person-years; 95% CI, 1.7 to 6.0); vaccine efficacy was 94.1% (95% CI, 89.3 to 96.8%; P<0.001). Efficacy was similar across key secondary analyses, including assessment 14 days after the first dose, analyses that included participants who had evidence of SARS-CoV-2 infection at baseline, and analyses in participants 65 years of age or older. Severe Covid-19 occurred in 30 participants, with one fatality; all 30 were in the placebo group. Moderate, transient reactogenicity after vaccination occurred more frequently in the mRNA-1273 group. Serious adverse events were rare, and the incidence was similar in the two groups.

CONCLUSIONS
The mRNA-1273 vaccine showed 94.1% efficacy at preventing Covid-19 illness, including severe disease. Aside from transient local and systemic reactions, no safety concerns were identified. (Funded by the Biomedical Advanced Research and Development Authority and the National Institute of Allergy and Infectious Diseases; COVE ClinicalTrials.gov number, NCT04470427. opens in new tab.)

QUICK TAKEEfficacy and Safety of mRNA-1273 SARS-CoV-2 Vaccine 02:31

The emergence in December 2019 of a novel coronavirus, the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), has had devastating consequences globally. Control measures such as the use of masks, physical distancing, testing of exposed or symptomatic persons, contact tracing, and isolation have helped limit the transmission where they have been rigorously applied; however, these actions have been variably implemented and have proved insufficient in impeding the spread of coronavirus disease 2019 (Covid-19), the disease caused by SARS-CoV-2. Vaccines are needed to reduce the morbidity and mortality associated with Covid-19, and multiple platforms have been involved in the rapid development of vaccine candidates.1-9


The mRNA vaccine platform has advantages as a pandemic-response strategy, given its flexibility and efficiency in immunogen design and manufacturing. Earlier work had suggested that the spike protein of the coronavirus responsible for the 2002 SARS outbreak was a suitable target for protective immunity.10 Numerous vaccine candidates in various stages of development are now being evaluated.11-13 Shortly after the SARS-CoV-2 genetic sequence was determined in January 2020, mRNA-1273, a lipid-nanoparticle (LNP)–encapsulated mRNA vaccine expressing the prefusion-stabilized spike glycoprotein, was developed by Moderna and the Vaccine Research Center at the National Institute of Allergy and Infectious Diseases (NIAID), within the National Institutes of Health (NIH).14 The mRNA-1273 vaccine demonstrated protection in animal-challenge experiments15 and encouraging safety and immunogenicity in early-stage human testing.1,4 The efficacy and safety of another mRNA vaccine, BNT162b2, was recently demonstrated.16

The Coronavirus Efficacy (COVE) phase 3 trial was launched in late July 2020 to assess the safety and efficacy of the mRNA-1273 vaccine in preventing SARS-CoV-2 infection. An independent data and safety monitoring board determined that the vaccine met the prespecified efficacy criteria at the first interim analysis. We report the primary analysis results of this ongoing pivotal phase 3 trial.

Methods
TRIAL OVERSIGHT
This phase 3 randomized, stratified, observer-blinded, placebo-controlled trial enrolled adults in medically stable condition at 99 U.S. sites. Participants received the first trial injection between July 27 and October 23, 2020. The trial is being conducted in accordance with the International Council for Harmonisation of Technical Requirements for Pharmaceuticals for Human Use, Good Clinical Practice guidelines, and applicable government regulations. The central institutional review board approved the protocol and the consent forms. All participants provided written informed consent before enrollment. Safety is reviewed by a protocol safety review team weekly and by an independent data and safety monitoring board on a continual basis. The trial Investigational New Drug sponsor, Moderna, was responsible for the overall trial design (with input from the Biomedical Advanced Research and Development Authority, the NIAID, the Covid-19 Prevention Network, and the trial cochairs), site selection and monitoring, and data analysis. Investigators are responsible for data collection. A medical writer funded by Moderna assisted in drafting the manuscript for submission. The authors vouch for the accuracy and completeness of the data and for the fidelity of the trial to the protocol. The trial is ongoing, and the investigators remain unaware of participant-level data. Designated team members within Moderna have unblinded access to the data, to facilitate interface with the regulatory agencies and the data and safety monitoring board; all other trial staff and participants remain unaware of the treatment assignments.

PARTICIPANTS, RANDOMIZATION, AND DATA BLINDING
Eligible participants were persons 18 years of age or older with no known history of SARS-CoV-2 infection and with locations or circumstances that put them at an appreciable risk of SARS-CoV-2 infection, a high risk of severe Covid-19, or both. Inclusion and exclusion criteria are provided in the protocol (available with the full text of this article at NEJM.org). To enhance the diversity of the trial population in accordance with Food and Drug Administration Draft Guidance, site-selection and enrollment processes were adjusted to increase the number of persons from racial and ethnic minorities in the trial, in addition to the persons at risk for SARS-CoV-2 infection in the local population. The upper limit for stratification of enrolled participants considered to be “at risk for severe illness” at screening was increased from 40% to 50%.17

Participants were randomly assigned in a 1:1 ratio, through the use of a centralized interactive response technology system, to receive vaccine or placebo. Assignment was stratified, on the basis of age and Covid-19 complications risk criteria, into the following risk groups: persons 65 years of age or older, persons younger than 65 years of age who were at heightened risk (at risk) for severe Covid-19, and persons younger than 65 years of age without heightened risk (not at risk). Participants younger than 65 years of age were categorized as having risk for severe Covid-19 if they had at least one of the following risk factors, based on the Centers for Disease Control and Prevention (CDC) criteria available at the time of trial design: chronic lung disease (e.g., emphysema, chronic bronchitis, idiopathic pulmonary fibrosis, cystic fibrosis, or moderate-to-severe asthma); cardiac disease (e.g., heart failure, congenital coronary artery disease, cardiomyopathies, or pulmonary hypertension); severe obesity (body mass index [the weight in kilograms divided by the square of the height in meters] ≥40); diabetes (type 1, type 2, or gestational); liver disease; or infection with the human immunodeficiency virus.18

Vaccine dose preparation and administration were performed by pharmacists and vaccine administrators who were aware of treatment assignments but had no other role in the conduct of the trial. Once the injection was completed, only trial staff who were unaware of treatment assignments performed assessments and interacted with the participants. Access to the randomization code was strictly controlled at the pharmacy. The data and safety monitoring board reviewed efficacy data at the group level and unblinded safety data at the participant level.

TRIAL VACCINE
The mRNA-1273 vaccine, provided as a sterile liquid at a concentration of 0.2 mg per milliliter, was administered by injection into the deltoid muscle according to a two-dose regimen. Injections were given 28 days apart, in the same arm, in a volume of 0.5 ml containing 100 μg of mRNA-1273 or saline placebo.1 Vaccine mRNA-1273 was stored at 2° to 8°C (35.6° to 46.4°F) at clinical sites before preparation and vaccination. No dilution was required. Doses could be held in syringes for up to 8 hours at room temperature before administration.

SAFETY ASSESSMENTS
Safety assessments included monitoring of solicited local and systemic adverse events for 7 days after each injection; unsolicited adverse reactions for 28 days after each injection; adverse events leading to discontinuation from a dose, from participation in the trial, or both; and medically attended adverse events and serious adverse events from day 1 through day 759. Adverse event grading criteria and toxicity tables are described in the protocol. Cases of Covid-19 and severe Covid-19 were continuously monitored by the data and safety monitoring board from randomization onward.

EFFICACY ASSESSMENTS
The primary end point was the efficacy of the mRNA-1273 vaccine in preventing a first occurrence of symptomatic Covid-19 with onset at least 14 days after the second injection in the per-protocol population, among participants who were seronegative at baseline. End points were judged by an independent adjudication committee that was unaware of group assignment. Covid-19 cases were defined as occurring in participants who had at least two of the following symptoms: fever (temperature ≥38°C), chills, myalgia, headache, sore throat, or new olfactory or taste disorder, or as occurring in those who had at least one respiratory sign or symptom (including cough, shortness of breath, or clinical or radiographic evidence of pneumonia) and at least one nasopharyngeal swab, nasal swab, or saliva sample (or respiratory sample, if the participant was hospitalized) that was positive for SARS-CoV-2 by reverse-transcriptase–polymerase-chain-reaction (RT-PCR) test. Participants were assessed for the presence of SARS-CoV-2–binding antibodies specific to the SARS-CoV-2 nucleocapsid protein (Roche Elecsys, Roche Diagnostics International) and had a nasopharyngeal swab for SARS-CoV-2 RT-PCR testing (Viracor, Eurofins Clinical Diagnostics) before each injection. SARS-CoV-2–infected volunteers were followed daily, to assess symptom severity, for 14 days or until symptoms resolved, whichever was longer. A nasopharyngeal swab for RT-PCR testing and a blood sample for identifying serologic evidence of SARS-CoV-2 infection were collected from participants with symptoms of Covid-19.

The consistency of vaccine efficacy at the primary end point was evaluated across various subgroups, including age groups (18 to <65 years of age and ≥65 years), age and health risk for severe disease (18 to <65 years and not at risk; 18 to <65 years and at risk; and ≥65 years), sex (female or male), race and ethnic group, and risk for severe Covid-19 illness. If the number of participants in a subgroup was too small, it was combined with other subgroups for the subgroup analyses.

A secondary end point was the efficacy of mRNA-1273 in the prevention of severe Covid-19 as defined by one of the following criteria: respiratory rate of 30 or more breaths per minute; heart rate at or exceeding 125 beats per minute; oxygen saturation at 93% or less while the participant was breathing ambient air at sea level or a ratio of the partial pressure of oxygen to the fraction of inspired oxygen below 300 mm Hg; respiratory failure; acute respiratory distress syndrome; evidence of shock (systolic blood pressure <90 mm Hg, diastolic blood pressure <60 mm Hg, or a need for vasopressors); clinically significant acute renal, hepatic, or neurologic dysfunction; admission to an intensive care unit; or death. Additional secondary end points included the efficacy of the vaccine at preventing Covid-19 after a single dose or at preventing Covid-19 according to a secondary (CDC), less restrictive case definition: having any symptom of Covid-19 and a positive SARS-CoV-2 test by RT-PCR (see Table S1 in the Supplementary Appendix, available at NEJM.org).

STATISTICAL ANALYSIS
For analysis of the primary end point, the trial was designed for the null hypothesis that the efficacy of the mRNA-1273 vaccine is 30% or less. A total of 151 cases of Covid-19 would provide 90% power to detect a 60% reduction in the hazard rate (i.e., 60% vaccine efficacy), with two planned interim analyses at approximately 35% and 70% of the target total number of cases (151) and with a one-sided O’Brien–Fleming boundary for efficacy and an overall one-sided error rate of 0.025. The efficacy of the mRNA-1273 vaccine could be demonstrated at either the interim or the primary analysis, performed when the target total number of cases had been observed. The Lan–DeMets alpha-spending function was used for calculating efficacy boundaries at each analysis. At the first interim analysis on November 15, 2020, vaccine efficacy had been demonstrated in accordance with the prespecified statistical criteria. The vaccine efficacy estimate, based on a total of 95 adjudicated cases (63% of the target total), was 94.5%, with a one-sided P value of less than 0.001 to reject the null hypothesis that vaccine efficacy would be 30% or less. The data and safety monitoring board recommendation to the oversight group and the trial sponsor was that the efficacy findings should be shared with the participants and the community (full details are available in the protocol and statistical analysis plan).

Vaccine efficacy was assessed in the full analysis population (randomized participants who received at least one dose of mRNA-1273 or placebo), the modified intention-to-treat population (participants in the full analysis population who had no immunologic or virologic evidence of Covid-19 on day 1, before the first dose), and the per-protocol population (participants in the modified intention-to-treat population who received two doses, with no major protocol deviations). The primary efficacy end point in the interim and primary analyses was assessed in the per-protocol population. Participants were evaluated in the treatment groups to which they were assigned. Vaccine efficacy was defined as the percentage reduction in the hazard ratio for the primary end point (mRNA-1273 vs. placebo). A stratified Cox proportional hazards model was used to assess the vaccine efficacy of mRNA-1273 as compared with placebo in terms of the percentage hazard reduction. (Details regarding the analysis of vaccine efficacy are provided in the Methods section of the Supplementary Appendix.)

Safety was assessed in all participants in the solicited safety population (i.e., those who received at least one injection and reported a solicited adverse event). Descriptive summary data (numbers and percentages) for participants with any solicited adverse events, unsolicited adverse events, unsolicited severe adverse events, serious adverse events, medically attended adverse events, and adverse events leading to discontinuation of the injections or withdrawal from the trial are provided by group. Two-sided 95% exact confidence intervals (Clopper–Pearson method) are provided for the percentages of participants with solicited adverse events. Unsolicited adverse events are presented according to the Medical Dictionary for Regulatory Activities (MedDRA), version 23.0, preferred terms and system organ class categories.

To meet the regulatory agencies’ requirement of a median follow-up duration of at least 2 months after completion of the two-dose regimen, a second analysis was performed, with an efficacy data cutoff date of November 21, 2020. This second analysis is considered the primary analysis of efficacy, with a total of 196 adjudicated Covid-19 cases in the per-protocol population, which exceeds the target total number of cases (151) specified in the protocol. This was an increase from the 95 cases observed at the first interim analysis data cutoff on November 11, 2020. Results from the primary analysis are presented in this report. Subsequent analyses are considered supplementary.

Results
TRIAL POPULATION
Figure 1.

Randomization and Analysis Populations.
Between July 27, 2020, and October 23, 2020, a total of 30,420 participants underwent randomization, and the 15,210 participants in each group were assigned to receive two doses of either placebo or mRNA-1273 (100 μg) (Figure 1). More than 96% of participants received the second dose (Fig. S1). Common reasons for not receiving the second dose were withdrawal of consent (153 participants) and the detection of SARS-CoV-2 by PCR before the administration of the second dose on day 29 (114 participants: 69 in the placebo group and 45 in the mRNA-1273 group). The primary efficacy and safety analyses were performed in the per-protocol and safety populations, respectively. Of the participants who received a first injection, 14,073 of those in the placebo group and 14,134 in the mRNA-1273 group were included in the primary efficacy analysis; 525 participants in the placebo group and 416 in the mRNA-1273 group were excluded from the per-protocol population, including those who had not received a second dose by the day 29 data cutoff (Figure 1). As of November 25, 2020, the participants had a median follow-up duration of 63 days (range, 0 to 97) after the second dose, with 62% of participants having more than 56 days of follow-up.

Table 1.

Demographic and Clinical Characteristics at Baseline.
Baseline demographic characteristics were balanced between the placebo group and the mRNA-1273 vaccine group (Table 1 and Table S2). The mean age of the participants was 51.4 years, 47.3% of the participants were female, 24.8% were 65 years of age or older, and 16.7% were younger than 65 years of age and had predisposing medical conditions that put them at risk for severe Covid-19. The majority of participants were White (79.2%), and the racial and ethnic proportions were generally representative of U.S. demographics, including 10.2% Black or African American and 20.5% Hispanic or Latino. Evidence of SARS-CoV-2 infection at baseline was present in 2.3% of participants in the mRNA-1273 group and in 2.2% in the placebo group, as detected by serologic assay or RT-PCR testing.

SAFETY
Figure 2.

Solicited Local and Systemic Adverse Events.
Solicited adverse events at the injection site occurred more frequently in the mRNA-1273 group than in the placebo group after both the first dose (84.2%, vs. 19.8%) and the second dose (88.6%, vs. 18.8%) (Figure 2and Tables S3 and S4). In the mRNA-1273 group, injection-site events were mainly grade 1 or 2 in severity and lasted a mean of 2.6 and 3.2 days after the first and second doses, respectively (Table S5). The most common injection-site event was pain after injection. Delayed injection-site reactions (those with onset on or after day 8) were noted in 244 participants (0.8%) after the first dose and in 68 participants (0.2%) after the second dose. Reactions were characterized by erythema, induration, and tenderness, and they resolved over the following 4 to 5 days. Solicited systemic adverse events occurred more often in the mRNA-1273 group than in the placebo group after both the first dose (54.9%, vs. 42.2%) and the second dose (79.4%, vs. 36.5%). The severity of the solicited systemic events increased after the second dose in the mRNA-1273 group, with an increase in proportions of grade 2 events (from 16.5% after the first dose to 38.1% after the second dose) and grade 3 events (from 2.9% to 15.8%). Solicited systemic adverse events in the mRNA-1273 group lasted a mean of 2.9 days and 3.1 days after the first and second doses, respectively (Table S5). Both solicited injection-site and systemic adverse events were more common among younger participants (18 to <65 years of age) than among older participants (≥65 years of age). Solicited adverse events were less common in participants who were positive for SARS-CoV-2 infection at baseline than in those who were negative at baseline (Tables S6 and S7).

The frequency of unsolicited adverse events, unsolicited severe adverse events, and serious adverse events reported during the 28 days after injection was generally similar among participants in the two groups (Tables S8 through S11). Three deaths occurred in the placebo group (one from intraabdominal perforation, one from cardiopulmonary arrest, and one from severe systemic inflammatory syndrome in a participant with chronic lymphocytic leukemia and diffuse bullous rash) and two in the vaccine group (one from cardiopulmonary arrest and one by suicide). The frequency of grade 3 adverse events in the placebo group (1.3%) was similar to that in the vaccine group (1.5%), as were the frequencies of medically attended adverse events (9.7% vs. 9.0%) and serious adverse events (0.6% in both groups). Hypersensitivity reactions were reported in 1.5% and 1.1% of participants in the vaccine and placebo groups, respectively (Table S12). Bell’s palsy occurred in the vaccine group (3 participants [<0.1%]) and the placebo group (1 participant [<0.1%]) during the observation period of the trial (more than 28 days after injection). Overall, 0.5% of participants in the placebo group and 0.3% in the mRNA-1273 group had adverse events that resulted in their not receiving the second dose, and less than 0.1% of participants in both groups discontinued participation in the trial because of adverse events after any dose (Table S8). No evidence of vaccine-associated enhanced respiratory disease was noted, and fewer cases of severe Covid-19 or any Covid-19 were observed among participants who received mRNA-1273 than among those who received placebo (Tables S13 and S14). Adverse events that were deemed by the trial team to be related to the vaccine or placebo were reported among 4.5% of participants in the placebo group and 8.2% in the mRNA-1273 group. The most common treatment-related adverse events (those reported in at least 1% of participants) in the placebo group and the mRNA-1273 group were fatigue (1.2% and 1.5%) and headache (0.9% and 1.4%). In the overall population, the incidence of treatment-related severe adverse events was higher in the mRNA-1273 group (71 participants [0.5%]) than in the placebo group (28 participants [0.2%]) (Tables S8 and S15). The relative incidence of these adverse events according to vaccine group was not affected by age.

EFFICACY
Figure 3.

Vaccine Efficacy of mRNA-1273 to Prevent Covid-19.
After day 1 and through November 25, 2020, a total of 269 Covid-19 cases were identified, with an incidence of 79.7 cases per 1000 person-years (95% confidence interval [CI], 70.5 to 89.9) among participants in the placebo group with no evidence of previous SARS-CoV-2 infection. For the primary analysis, 196 cases of Covid-19 were diagnosed: 11 cases in the vaccine group (3.3 per 1000 person-years; 95% CI, 1.7 to 6.0) and 185 cases in the placebo group (56.5 per 1000 person-years; 95% CI, 48.7 to 65.3), indicating 94.1% efficacy of the mRNA-1273 vaccine (95% CI, 89.3 to 96.8%; P<0.001) for the prevention of symptomatic SARS-CoV-2 infection as compared with placebo (Figure 3A). Findings were similar across key secondary analyses (Table S16), including assessment starting 14 days after dose 1 (225 cases with placebo, vs. 11 with mRNA-1273, indicating a vaccine efficacy of 95.2% [95% CI, 91.2 to 97.4]), and assessment including participants who were SARS-CoV-2 seropositive at baseline in the per-protocol analysis (187 cases with placebo, vs. 12 with mRNA-1273; one volunteer assigned to receive mRNA-1273 was inadvertently given placebo], indicating a vaccine efficacy of 93.6% [95% CI, 88.6 to 96.5]). Between days 1 and 42, seven cases of Covid-19 were identified in the mRNA-1273 group, as compared with 65 cases in the placebo group (Figure 3B).

Figure 4.

Vaccine Efficacy of mRNA-1273 to Prevent Covid-19 in Subgroups.
A key secondary end point evaluated the efficacy of mRNA-1273 at preventing severe Covid-19. Thirty participants in the trial had severe Covid-19; all 30 were in the placebo group (indicating vaccine efficacy of 100% [95% CI, could not be estimated to 1.0]), and one death among these participants was attributed to Covid-19 (Table S16). The vaccine efficacy to prevent Covid-19 was consistent across subgroups stratified by demographic and baseline characteristics (Figure 4): age groups (18 to <65 years of age and ≥65 years), presence of risk for severe Covid-19, sex, and race and ethnic group (non-Hispanic White and communities of color). Among participants who were positive for SARS-CoV-2, by serologic or virologic testing, at baseline (337 in the placebo group and 343 in the mRNA-1273 group), one case of Covid-19 was diagnosed by RT-PCR testing in a placebo recipient and no cases were diagnosed in mRNA-1273 recipients (Table S17). Among participants who were negative for SARS-CoV-2 at baseline (by RT-PCR or antibody testing), in addition to symptomatic Covid-19 cases 39 (0.3%) in the placebo group and 15 (0.1%) in the mRNA-1273 group had nasopharyngeal swabs that were positive for SARS-CoV-2 by RT-PCR at the second dose visit (surveillance swab) but had no evidence of Covid-19 symptoms (Table S18).

Discussion
The COVE trial provides evidence of short-term efficacy of the mRNA-1273 vaccine in preventing symptomatic SARS-CoV-2 infection in a diverse adult trial population. Of note, the trial was designed for an infection attack rate of 0.75%, which would have necessitated a follow-up period of 6 months after the two vaccine doses to accrue 151 cases in 30,000 participants. The pandemic trajectory accelerated in many U.S. regions in the late summer and fall of 2020, resulting in rapid accrual of 196 cases after a median follow-up of 2 months. It is important to note that all the severe Covid-19 cases were in the placebo group, which suggests that mRNA-1273 is likely to have an effect on preventing severe illness, which is the major cause of health care utilization, complications, and death. The finding of fewer occurrences of symptomatic SARS-CoV-2 infection after a single dose of mRNA-1273 is encouraging; however, the trial was not designed to evaluate the efficacy of a single dose, and additional evaluation is warranted.

The magnitude of mRNA-1273 vaccine efficacy at preventing symptomatic SARS-CoV-2 infection is higher than the efficacy observed for vaccines for respiratory viruses, such as the inactivated influenza vaccine against symptomatic, virologically confirmed disease in adults, for which studies have shown a pooled efficacy of 59%.19 This high apparent efficacy of mRNA-1273 is based on short-term data, and waning of efficacy over time has been demonstrated with other vaccines.20 Also, the efficacy of the vaccine was tested in a setting of national recommendations for masking and social distancing, which may have translated into lower levels of infectious inoculum. The efficacy of mRNA-1273 is in line with that of the recently reported BNT162b2 mRNA vaccine.16 The COVE trial is ongoing, and longitudinal follow-up will allow an assessment of efficacy changes over time and under evolving epidemiologic conditions.

Overall, the safety of the mRNA-1273 vaccine regimen and platform is reassuring; no unexpected patterns of concern were identified. The reactogenicity associated with immunization with mRNA-1273 in this trial is similar to that in the phase 1 data reported previously.1,4 Overall, the local reactions to vaccination were mild; however, moderate-to-severe systemic side effects, such as fatigue, myalgia, arthralgia, and headache, were noted in about 50% of participants in the mRNA-1273 group after the second dose. These side effects were transient, starting about 15 hours after vaccination and resolving in most participants by day 2, without sequelae. The degree of reactogenicity after one dose of mRNA-1273 was less than that observed for the recently approved recombinant adjuvanted zoster vaccine and after the second mRNA-1273 dose was similar to that of the zoster vaccine.21,22 Delayed injection-site reactions, with an onset 8 days or more after injection, were uncommon. The overall incidence of unsolicited adverse events reported up to 28 days after vaccination and of serious adverse events reported throughout the entire trial was similar for mRNA-1273 and placebo. A risk of acute hypersensitivity is sometimes observed with vaccines; however, no such risk was evident in the COVE trial, although the ability to detect rare events is limited, given the trial sample size. The anecdotal finding of a slight excess of Bell’s palsy in this trial and in the BNT162b2 vaccine trial arouses concern that it may be more than a chance event, and the possibility bears close monitoring.16

The mRNA-1273 vaccine did not show evidence in the short term of enhanced respiratory disease after infection, a concern that emerged from animal models used in evaluating some SARS and Middle East respiratory syndrome (MERS) vaccine constructs.23-25 A hallmark of enhanced respiratory disease is a Th2-skewed immune response and eosinophilic pulmonary infiltration on histopathological examination. Of note, preclinical testing of mRNA-1273 and other SARS-CoV-2 vaccines in advanced clinical evaluation has shown a Th1-skewed vaccine response and no pathologic lung infiltrates.15,26-28Whether mRNA-1273 vaccination results in enhanced disease on exposure to the virus in the long term is unknown.

Key limitations of the data are the short duration of safety and efficacy follow-up. The trial is ongoing, and a follow-up duration of 2 years is planned, with possible changes to the trial design to allow participant retention and ongoing data collection. Another limitation is the lack of an identified correlate of protection, a critical tool for future bridging studies. As of the data cutoff, 11 cases of Covid-19 had occurred in the mRNA-1273 group, a finding that limits our ability to detect a correlate of protection. As cases accrue and immunity wanes, it may become possible to determine such a correlate. In addition, although our trial showed that mRNA-1273 reduces the incidence of symptomatic SARS-CoV-2 infection, the data were not sufficient to assess asymptomatic infection, although our results from a preliminary exploratory analysis suggest that some degree of prevention may be afforded after the first dose. Evaluation of the incidence of asymptomatic or subclinical infection and viral shedding after infection are under way, to assess whether vaccination affects infectiousness. The relatively smaller numbers of cases that occurred in older adults and in participants from ethnic or racial minorities and the small number of previously infected persons who received the vaccine limit efficacy evaluations in these groups. Longer-term data from the ongoing trial may allow a more careful evaluation of the vaccine efficacy in these groups. Pregnant women and children were excluded from this trial, and additional evaluation of the vaccine in these groups is planned.

Within 1 year after the emergence of this novel infection that caused a pandemic, a pathogen was determined, vaccine targets were identified, vaccine constructs were created, manufacturing to scale was developed, phase 1 through phase 3 testing was conducted, and data have been reported. This process demonstrates what is possible in the context of motivated collaboration among key sectors of society, including academia, government, industry, regulators, and the larger community. Lessons learned from this endeavor should allow us to better prepare for the next pandemic pathogen.

Supported by the Office of the Assistant Secretary for Preparedness and Response, Biomedical Advanced Research and Development Authority (contract 75A50120C00034) and by the National Institute of Allergy and Infectious Diseases (NIAID). The NIAID provides grant funding to the HIV Vaccine Trials Network (HVTN) Leadership and Operations Center (UM1 AI 68614HVTN), the Statistics and Data Management Center (UM1 AI 68635), the HVTN Laboratory Center (UM1 AI 68618), the HIV Prevention Trials Network Leadership and Operations Center (UM1 AI 68619), the AIDS Clinical Trials Group Leadership and Operations Center (UM1 AI 68636), and the Infectious Diseases Clinical Research Consortium leadership group 5 (UM1 AI148684-03).

Disclosure forms provided by the authors are available with the full text of this article at NEJM.org.

Dr. Baden reports being funded by the NIH to conduct clinical trials in collaboration with Crucell/Janssen and Moderna; Dr. Rouphael, receiving grant support from Pfizer, Merck, Sanofi–Pasteur, Eli Lilly, and Quidel; Dr. Creech, receiving grant support from Merck, consulting fees from Horizon Pharma and GSK, and fees for serving on a data and safety monitoring board from Astellas; Dr. Neuzil, receiving grant support from Pfizer; Dr. Graham, holding pending patent WO/2018/081318 on prefusion coronavirus spike proteins and their use and pending patent 62/972,886 on 2019-nCoV vaccine; Dr. Bennett, being employed by and owning stock and stock options in Moderna; Dr. Pajon, being employed by and owning stock in Moderna; Dr. Knightly, being employed by and owning stock and stock options in Moderna; Drs. Leav, Deng, and Zhou being employees of Moderna; Dr. Han, being employed by and owning stock and stock options in Moderna; Dr. Ivarsson, being employed by and owning share options in Moderna; Dr. Miller, being employed by and owning stock and stock options in Moderna; and Dr. Zaks, being employed by and owning stock options in Moderna. No other potential conflict of interest relevant to this article was reported.

Drs. Baden and El Sahly contributed equally to this article.

This article was published on December 30, 2020, and updated on January 15, 2021, at NEJM.org.

A data sharing statement provided by the authors is available with the full text of this article at NEJM.org.

We thank the participants in the trial and the members of the mRNA-1273 trial team (listed in the Supplementary Appendix) for their dedication and the contributions to the trial, and the members of the data and safety monitoring board (Richard J. Whitley [chair], University of Alabama School of Medicine; Abdel Babiker, MRC Clinical Trials Unit at University College, London; Lisa A. Cooper, Johns Hopkins University School of Medicine and Bloomberg School of Public Health; Susan S. Ellenberg, University of Pennsylvania; Alan Fix, Vaccine Development Global Program Center for Vaccine Innovation and Access PATH; Marie Griffin, Vanderbilt University Medical Center; Steven Joffe, Perelman School of Medicine, University of Pennsylvania; Jorge Kalil, Heart Institute, Hospital das Clínicas da Faculdade de Medicina da Universidade de São Paulo; Myron M. Levine, University of Maryland School of Medicine; Malegapuru W. Makgoba, University of KwaZulu-Natal; Anastasios A. Tsiatis, North Carolina State University; Renee H. Moore, Emory University); and Sally Hunsberger [Executive Secretary], NIAID) for their hard work, support, and guidance of the trial; and the adjudication committee (Richard J. Hamill [chair], Baylor College of Medicine; Lewis Lipsitz, Harvard Medical School; Eric S. Rosenberg, Massachusetts General Hospital; and Anthony Faugno, Tufts Medical Center) for their critical and timely review of the trial data. We also acknowledge the contribution from the mRNA-1273 Product Coordination Team from the Biomedical Advanced Research and Development Authority (BARDA) (Robert Bruno, Richard Gorman, Holli Hamilton, Gary Horwith, Chuong Huynh, Nutan Mytle, Corrina Pavetto, Xiaomi Tong, and John Treanor), and Joanne E. Tomassini (JET Scientific), for assistance in writing the manuscript for submission, and Frank J. Dutko, for editorial support (funded by Moderna).

Author Affiliations
From Brigham and Women’s Hospital (L.R.B.), Boston, and Moderna, Cambridge (H.B., R.P., C.K., B.L., W.D., H.Z., S.H., M.I., J. Miller, T.Z.) — both in Massachusetts; Baylor College of Medicine (H.M.E.S.) and Centex Studies (J.S.) — both in Houston; Meridian Clinical Research, Savannah (B.E., S.K., A.B.), and Emory University (N.R.) and Atlanta Clinical Research Center (N.S.), Atlanta — all in Georgia; University of Maryland School of Medicine, Baltimore (K.K., K.N.), and National Institute of Allergy and Infectious Diseases, Bethesda (D.F., M.M., J. Mascola, L.P., J.L., B.S.G.) — both in Maryland; Saint Louis University School of Medicine, St. Louis (S.F.); University of Illinois, Chicago, Chicago (R.N.); George Washington University School of Medicine and Health Sciences, Washington, DC (D.D.); University of California, San Diego, San Diego (S.A.S.); Vanderbilt University School of Medicine, Nashville (C.B.C.); Quality of Life Medical and Research Center, Tucson, AZ (J. McGettigan); Johnson County Clin-Trials, Lenexa, KS (C.F.); Research Centers of America, Hollywood, FL (H.S.); and Fred Hutchinson Cancer Research Center, Seattle (L.C., P.G., H.J.).

Address reprint requests to Dr. El Sahly at the Departments of Molecular Virology and Microbiology and Medicine, 1 Baylor Plaza, BCM-MS280, Houston, TX 77030, or at [email protected]; or to Dr. Baden at the Division of Infectious Diseases, Brigham and Women’s Hospital, 15 Francis St., PBB-A4, Boston, MA 02115, or at [email protected].

A complete list of members of the COVE Study Group is provided in the Supplementary Appendix, available at NEJM.org.



Supplementary Material
Protocol PDF 2563KB
Supplementary Appendix PDF 1057KB
Disclosure Forms PDF 644KB
Data Sharing Statement PDF 70KB
Research Summary PDF 3598KB

References (28)

1. 1.
   
   • . opens in new tab
   • . opens in new tab
     . opens in new tab
2. 2.
   
   • . opens in new tab
   • . opens in new tab
     . opens in new tab
3. 3.
   
   • . opens in new tab
   • . opens in new tab
     . opens in new tab
4. 4.
   
   • . opens in new tab
   • . opens in new tab
     . opens in new tab
5. 5.
   
   • . opens in new tab
   • . opens in new tab
   • . opens in new tab
     . opens in new tab
6. 6.
   
   • . opens in new tab
   • . opens in new tab
   • . opens in new tab
     . opens in new tab
7. 7.
   
   • . opens in new tab
   • . opens in new tab
   • . opens in new tab
     . opens in new tab
8. 8.
   
   • . opens in new tab
   • . opens in new tab
   • . opens in new tab
     . opens in new tab
9. 9.
   
   • . opens in new tab
   • . opens in new tab
     . opens in new tab
10. 10.
    
    • . opens in new tab
    • . opens in new tab
    • . opens in new tab
      . opens in new tab
11. 11.
    
    • . opens in new tab
    • . opens in new tab
    • . opens in new tab
      . opens in new tab
12. 12.
    
    • . opens in new tab
    • . opens in new tab
      . opens in new tab
13. 13.
    
    • . opens in new tab
    • . opens in new tab
    • . opens in new tab
      . opens in new tab
14. 14. . opens in new tab
    
    • 
      . opens in new tab
15. 15.
    
    • . opens in new tab
    • . opens in new tab
      . opens in new tab
16. 16.
    
    • . opens in new tab
    • . opens in new tab
      . opens in new tab
17. 17. . opens in new tab
    
    • 
      . opens in new tab
18. 18. . opens in new tab
    
    • 
      . opens in new tab
19. 19.
    
    • . opens in new tab
    • . opens in new tab
    • . opens in new tab
      . opens in new tab
20. 20.
    
    • . opens in new tab
    • . opens in new tab
    • . opens in new tab
      . opens in new tab
21. 21.
    
    • . opens in new tab
    • . opens in new tab
      . opens in new tab
22. 22.
    
    • . opens in new tab
    • . opens in new tab
      . opens in new tab
23. 23.
    
    • . opens in new tab
    • . opens in new tab
    • . opens in new tab
      . opens in new tab
24. 24.
    
    • . opens in new tab
    • . opens in new tab
    • . opens in new tab
      . opens in new tab
25. 25.
    
    • . opens in new tab
    • . opens in new tab
    • . opens in new tab
      . opens in new tab
26. 26.
    
    • . opens in new tab
    • . opens in new tab
    • . opens in new tab
      . opens in new tab
27. 27.
    
    • . opens in new tab
    • . opens in new tab
    • . opens in new tab
      . opens in new tab
28. 28. . opens in new tab
    
    • 
      . opens in new tab

Citing Articles (62)

Comments (9)

1. Download a PDF of the Research Summary.
   
   
2. Figure 1. Randomization and Analysis Populations.
   
   The data cutoff for the primary analysis occurred on November 25, 2020. The full analysis population consisted of participants who underwent randomization and received at least one dose of mRNA-1273 or placebo; the modified intention-to-treat population comprised participants in the full analysis population who had no immunologic or virologic evidence of Covid-19 on day 1, before the first dose; and the per-protocol analysis population included participants in the modified intention-to-treat population who received two doses, with no major protocol deviations. The safety population included all participants who received at least one injection. Among participants who received an incorrect injection, three participants in the mRNA-1273 group received at least one dose of placebo and no dose of mRNA-1273 and were included in the placebo safety population, and three received one dose of placebo and one dose of mRNA-1273 and were included in the mRNA-1273 safety population; in the placebo group all seven received mRNA-1273 and were included in the mRNA-1273 safety population. Participants who received dose 2 outside the window for the per-protocol analysis are those who did not receive the second dose between 7 days before and 14 days after day 29.
   
3. Table 1. Demographic and Clinical Characteristics at Baseline.*
   
4. Figure 2. Solicited Local and Systemic Adverse Events.
   
   Shown is the percentage of participants who had a solicited local or systemic adverse event within 7 days after injection 1 or injection 2 of either the placebo or the mRNA-1273 vaccine.
   
5. Figure 3. Vaccine Efficacy of mRNA-1273 to Prevent Covid-19.
   
   Shown is the cumulative incidence of Covid-19 events in the primary analysis based on adjudicated assessment starting 14 days after the second vaccination in the per-protocol population (Panel A) and after randomization in the modified intention-to-treat population (Panel B) (see the Supplementary Appendix). The dotted line in Panel A indicates day 42 (14 days after vaccination 2), when the per-protocol follow-up began, and arrows in both panels indicate days 1 and 29, when injections were administered. Tick marks indicate censored data. Vaccine efficacy was defined as 1 minus the hazard ratio (mRNA vs. placebo), and the 95% confidence interval was estimated with the use of a stratified Cox proportional hazards model, with Efron’s method of tie handling and with treatment group as a covariate, with adjustment for stratification factor. Incidence was defined as the number of events divided by number of participants at risk and was adjusted by person-years. Symptomatic Covid-19 case accrual for placebo and vaccine in the modified intention-to-treat population is displayed (does not include asymptomatic cases of SARS-CoV-2 detected at the day 29 by nasopharyngeal swab).
   
   
6. Figure 4. Vaccine Efficacy of mRNA-1273 to Prevent Covid-19 in Subgroups.
   
   The efficacy of the RNA-1273 vaccine in preventing Covid-19 in various subgroups in the per-protocol population was based on adjudicated assessments starting 14 days after the second injection. Vaccine efficacy, defined as 1 minus the hazard ratio (mRNA-1273 vs. placebo), and 95% confidence intervals were estimated with the use of a stratified Cox proportional hazards model, with Efron’s method of tie handling and with the treatment group as a covariate, adjusting for stratification factor if applicable. Race and ethnic group categories shown are White (non-Hispanic) and communities of color (all others, excluding those whose race and ethnicity were both reported as unknown, were not reported, or were both missing at screening). Data for communities of color were pooled owing to limited numbers of participants in each racial or ethnic group, to ensure that the subpopulations would be large enough for meaningful analyses.
   

• Article
• Figures/Media

 

[JD8]

The Moderna COVID-19 (mRNA-1273) vaccine: what you need to know
https://www.who.int/

Does it prevent infection and transmission?
We do not know whether the vaccine will prevent infection and protect against onward transmission. Immunity persists for several months, but the full duration is not yet known. These important questions are being studied.

In the meantime, we must maintain public health measures that work: masking, physical distancing, handwashing, respiratory and cough hygiene, avoiding crowds, and ensuring good ventilation.

Is it safe?
While this vaccine has yet to be approved by WHO for an Emergency Use Listing

Those who experience an immediate severe allergic reaction to the first dose should not receive additional doses.

Longer-term safety assessment involves continued follow up of clinical trial participants, as well as specific studies and continued surveillance of secondary effects or adverse events of those being vaccinated in the roll out.



more of your ignorance showing ... ha ha ha
do you even bother reading before you post?
a better question is ... do you even understand the topic?
based on your two responses .. you really don't understand.

your article flat doesn't cover the two questions brought up.

Does it prevent infection and transmission?

Is it safe?

I can't help it if you didn't read what I posted, nor could understand it. Probably too many big words??

I get it though, you're not used to reading facts or real science.

https://www.nejm.org/doi/full/10.1056/NEJMoa2034577

Safety and Efficacy of the BNT162b2 mRNA Covid-19 Vaccine
List of authors.

• Fernando P. Polack, M.D.,
• Stephen J. Thomas, M.D.,
• Nicholas Kitchin, M.D.,
• Judith Absalon, M.D.,
• Alejandra Gurtman, M.D.,
• Stephen Lockhart, D.M.,
• John L. Perez, M.D.,
• Gonzalo Pérez Marc, M.D.,
• Edson D. Moreira, M.D.,
• Cristiano Zerbini, M.D.,
• Ruth Bailey, B.Sc.,
• Kena A. Swanson, Ph.D.,
• for the C4591001 Clinical Trial Group*

• Article
• Figures/Media

Metrics

• 13 References
• 200 Citing Articles
• Letters
  Abstract
  BACKGROUND
  Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection and the resulting coronavirus disease 2019 (Covid-19) have afflicted tens of millions of people in a worldwide pandemic. Safe and effective vaccines are needed urgently.
  
  METHODS
  
  
  
  In an ongoing multinational, placebo-controlled, observer-blinded, pivotal efficacy trial, we randomly assigned persons 16 years of age or older in a 1:1 ratio to receive two doses, 21 days apart, of either placebo or the BNT162b2 vaccine candidate (30 μg per dose). BNT162b2 is a lipid nanoparticle–formulated, nucleoside-modified RNA vaccine that encodes a prefusion stabilized, membrane-anchored SARS-CoV-2 full-length spike protein. The primary end points were efficacy of the vaccine against laboratory-confirmed Covid-19 and safety.
  
  RESULTS
  A total of 43,548 participants underwent randomization, of whom 43,448 received injections: 21,720 with BNT162b2 and 21,728 with placebo. There were 8 cases of Covid-19 with onset at least 7 days after the second dose among participants assigned to receive BNT162b2 and 162 cases among those assigned to placebo; BNT162b2 was 95% effective in preventing Covid-19 (95% credible interval, 90.3 to 97.6). Similar vaccine efficacy (generally 90 to 100%) was observed across subgroups defined by age, sex, race, ethnicity, baseline body-mass index, and the presence of coexisting conditions. Among 10 cases of severe Covid-19 with onset after the first dose, 9 occurred in placebo recipients and 1 in a BNT162b2 recipient. The safety profile of BNT162b2 was characterized by short-term, mild-to-moderate pain at the injection site, fatigue, and headache. The incidence of serious adverse events was low and was similar in the vaccine and placebo groups.
  
  CONCLUSIONS
  A two-dose regimen of BNT162b2 conferred 95% protection against Covid-19 in persons 16 years of age or older. Safety over a median of 2 months was similar to that of other viral vaccines. (Funded by BioNTech and Pfizer; ClinicalTrials.gov number, NCT04368728. opens in new tab.)
  
  QUICK TAKESafety and Efficacy of the BNT162b2 Covid-19 Vaccine 03:00
  
  Coronavirus disease 2019 (Covid-19) has affected tens of millions of people globally1 since it was declared a pandemic by the World Health Organization on March 11, 2020.2 Older adults, persons with certain coexisting conditions, and front-line workers are at highest risk for Covid-19 and its complications. Recent data show increasing rates of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection and Covid-19 in other populations, including younger adults.3 Safe and effective prophylactic vaccines are urgently needed to contain the pandemic, which has had devastating medical, economic, and social consequences.
  
  
  We previously reported phase 1 safety and immunogenicity results from clinical trials of the vaccine candidate BNT162b2,4 a lipid nanoparticle–formulated,5 nucleoside-modified RNA (modRNA)6encoding the SARS-CoV-2 full-length spike, modified by two proline mutations to lock it in the prefusion conformation.7 Findings from studies conducted in the United States and Germany among healthy men and women showed that two 30-μg doses of BNT162b2 elicited high SARS-CoV-2 neutralizing antibody titers and robust antigen-specific CD8+ and Th1-type CD4+ T-cell responses.8 The 50% neutralizing geometric mean titers elicited by 30 μg of BNT162b2 in older and younger adults exceeded the geometric mean titer measured in a human convalescent serum panel, despite a lower neutralizing response in older adults than in younger adults. In addition, the reactogenicity profile of BNT162b2 represented mainly short-term local (i.e., injection site) and systemic responses. These findings supported progression of the BNT162b2 vaccine candidate into phase 3.
  
  Here, we report safety and efficacy findings from the phase 2/3 part of a global phase 1/2/3 trial evaluating the safety, immunogenicity, and efficacy of 30 μg of BNT162b2 in preventing Covid-19 in persons 16 years of age or older. This data set and these trial results are the basis for an application for emergency use authorization.9 Collection of phase 2/3 data on vaccine immunogenicity and the durability of the immune response to immunization is ongoing, and those data are not reported here.
  
  Methods
  TRIAL OBJECTIVES, PARTICIPANTS AND OVERSIGHT
  We assessed the safety and efficacy of two 30-μg doses of BNT162b2, administered intramuscularly 21 days apart, as compared with placebo. Adults 16 years of age or older who were healthy or had stable chronic medical conditions, including but not limited to human immunodeficiency virus (HIV), hepatitis B virus, or hepatitis C virus infection, were eligible for participation in the trial. Key exclusion criteria included a medical history of Covid-19, treatment with immunosuppressive therapy, or diagnosis with an immunocompromising condition.
  
  Pfizer was responsible for the design and conduct of the trial, data collection, data analysis, data interpretation, and the writing of the manuscript. BioNTech was the sponsor of the trial, manufactured the BNT162b2 clinical trial material, and contributed to the interpretation of the data and the writing of the manuscript. All the trial data were available to all the authors, who vouch for its accuracy and completeness and for adherence of the trial to the protocol, which is available with the full text of this article at NEJM.org. An independent data and safety monitoring board reviewed efficacy and unblinded safety data.
  
  TRIAL PROCEDURES
  With the use of an interactive Web-based system, participants in the trial were randomly assigned in a 1:1 ratio to receive 30 μg of BNT162b2 (0.3 ml volume per dose) or saline placebo. Participants received two injections, 21 days apart, of either BNT162b2 or placebo, delivered in the deltoid muscle. Site staff who were responsible for safety evaluation and were unaware of group assignments observed participants for 30 minutes after vaccination for any acute reactions.
  
  SAFETY
  The primary end points of this trial were solicited, specific local or systemic adverse events and use of antipyretic or pain medication within 7 days after the receipt of each dose of vaccine or placebo, as prompted by and recorded in an electronic diary in a subset of participants (the reactogenicity subset), and unsolicited adverse events (those reported by the participants without prompts from the electronic diary) through 1 month after the second dose and unsolicited serious adverse events through 6 months after the second dose. Adverse event data through approximately 14 weeks after the second dose are included in this report. In this report, safety data are reported for all participants who provided informed consent and received at least one dose of vaccine or placebo. Per protocol, safety results for participants infected with HIV (196 patients) will be analyzed separately and are not included here.
  
  During the phase 2/3 portion of the study, a stopping rule for the theoretical concern of vaccine-enhanced disease was to be triggered if the one-sided probability of observing the same or a more unfavorable adverse severe case split (a split with a greater proportion of severe cases in vaccine recipients) was 5% or less, given the same true incidence for vaccine and placebo recipients. Alert criteria were to be triggered if this probability was less than 11%.
  
  EFFICACY
  The first primary end point was the efficacy of BNT162b2 against confirmed Covid-19 with onset at least 7 days after the second dose in participants who had been without serologic or virologic evidence of SARS-CoV-2 infection up to 7 days after the second dose; the second primary end point was efficacy in participants with and participants without evidence of prior infection. Confirmed Covid-19 was defined according to the Food and Drug Administration (FDA) criteria as the presence of at least one of the following symptoms: fever, new or increased cough, new or increased shortness of breath, chills, new or increased muscle pain, new loss of taste or smell, sore throat, diarrhea, or vomiting, combined with a respiratory specimen obtained during the symptomatic period or within 4 days before or after it that was positive for SARS-CoV-2 by nucleic acid amplification–based testing, either at the central laboratory or at a local testing facility (using a protocol-defined acceptable test).
  
  Major secondary end points included the efficacy of BNT162b2 against severe Covid-19. Severe Covid-19 is defined by the FDA as confirmed Covid-19 with one of the following additional features: clinical signs at rest that are indicative of severe systemic illness; respiratory failure; evidence of shock; significant acute renal, hepatic, or neurologic dysfunction; admission to an intensive care unit; or death. Details are provided in the protocol.
  
  An explanation of the various denominator values for use in assessing the results of the trial is provided in Table S1 in the Supplementary Appendix, available at NEJM.org. In brief, the safety population includes persons 16 years of age or older; a total of 43,448 participants constituted the population of enrolled persons injected with the vaccine or placebo. The main safety subset as defined by the FDA, with a median of 2 months of follow-up as of October 9, 2020, consisted of 37,706 persons, and the reactogenicity subset consisted of 8183 persons. The modified intention-to-treat (mITT) efficacy population includes all age groups 12 years of age or older (43,355 persons; 100 participants who were 12 to 15 years of age contributed to person-time years but included no cases). The number of persons who could be evaluated for efficacy 7 days after the second dose and who had no evidence of prior infection was 36,523, and the number of persons who could be evaluated 7 days after the second dose with or without evidence of prior infection was 40,137.
  
  STATISTICAL ANALYSIS
  The safety analyses included all participants who received at least one dose of BNT162b2 or placebo. The findings are descriptive in nature and not based on formal statistical hypothesis testing. Safety analyses are presented as counts, percentages, and associated Clopper–Pearson 95% confidence intervals for local reactions, systemic events, and any adverse events after vaccination, according to terms in the Medical Dictionary for Regulatory Activities (MedDRA), version 23.1, for each vaccine group.
  
  Analysis of the first primary efficacy end point included participants who received the vaccine or placebo as randomly assigned, had no evidence of infection within 7 days after the second dose, and had no major protocol deviations (the population that could be evaluated). Vaccine efficacy was estimated by 100×(1−IRR), where IRR is the calculated ratio of confirmed cases of Covid-19 illness per 1000 person-years of follow-up in the active vaccine group to the corresponding illness rate in the placebo group. The 95.0% credible interval for vaccine efficacy and the probability of vaccine efficacy greater than 30% were calculated with the use of a Bayesian beta-binomial model. The final analysis uses a success boundary of 98.6% for probability of vaccine efficacy greater than 30% to compensate for the interim analysis and to control the overall type 1 error rate at 2.5%. Moreover, primary and secondary efficacy end points are evaluated sequentially to control the familywise type 1 error rate at 2.5%. Descriptive analyses (estimates of vaccine efficacy and 95% confidence intervals) are provided for key subgroups.
  
  Results
  PARTICIPANTS
  Figure 1.
  
  Enrollment and Randomization.Table 1.
  
  Demographic Characteristics of the Participants in the Main Safety Population.
  Between July 27, 2020, and November 14, 2020, a total of 44,820 persons were screened, and 43,548 persons 16 years of age or older underwent randomization at 152 sites worldwide (United States, 130 sites; Argentina, 1; Brazil, 2; South Africa, 4; Germany, 6; and Turkey, 9) in the phase 2/3 portion of the trial. A total of 43,448 participants received injections: 21,720 received BNT162b2 and 21,728 received placebo (Figure 1). At the data cut-off date of October 9, a total of 37,706 participants had a median of at least 2 months of safety data available after the second dose and contributed to the main safety data set. Among these 37,706 participants, 49% were female, 83% were White, 9% were Black or African American, 28% were Hispanic or Latinx, 35% were obese (body mass index [the weight in kilograms divided by the square of the height in meters] of at least 30.0), and 21% had at least one coexisting condition. The median age was 52 years, and 42% of participants were older than 55 years of age (Table 1 and Table S2).
  
  SAFETY
  Local Reactogenicity
  Figure 2.
  
  Local and Systemic Reactions Reported within 7 Days after Injection of BNT162b2 or Placebo, According to Age Group.
  The reactogenicity subset included 8183 participants. Overall, BNT162b2 recipients reported more local reactions than placebo recipients. Among BNT162b2 recipients, mild-to-moderate pain at the injection site within 7 days after an injection was the most commonly reported local reaction, with less than 1% of participants across all age groups reporting severe pain (Figure 2). Pain was reported less frequently among participants older than 55 years of age (71% reported pain after the first dose; 66% after the second dose) than among younger participants (83% after the first dose; 78% after the second dose). A noticeably lower percentage of participants reported injection-site redness or swelling. The proportion of participants reporting local reactions did not increase after the second dose (Figure 2A), and no participant reported a grade 4 local reaction. In general, local reactions were mostly mild-to-moderate in severity and resolved within 1 to 2 days.
  
  Systemic Reactogenicity
  Systemic events were reported more often by younger vaccine recipients (16 to 55 years of age) than by older vaccine recipients (more than 55 years of age) in the reactogenicity subset and more often after dose 2 than dose 1 (Figure 2B). The most commonly reported systemic events were fatigue and headache (59% and 52%, respectively, after the second dose, among younger vaccine recipients; 51% and 39% among older recipients), although fatigue and headache were also reported by many placebo recipients (23% and 24%, respectively, after the second dose, among younger vaccine recipients; 17% and 14% among older recipients). The frequency of any severe systemic event after the first dose was 0.9% or less. Severe systemic events were reported in less than 2% of vaccine recipients after either dose, except for fatigue (in 3.8%) and headache (in 2.0%) after the second dose.
  
  Fever (temperature, ≥38°C) was reported after the second dose by 16% of younger vaccine recipients and by 11% of older recipients. Only 0.2% of vaccine recipients and 0.1% of placebo recipients reported fever (temperature, 38.9 to 40°C) after the first dose, as compared with 0.8% and 0.1%, respectively, after the second dose. Two participants each in the vaccine and placebo groups reported temperatures above 40.0°C. Younger vaccine recipients were more likely to use antipyretic or pain medication (28% after dose 1; 45% after dose 2) than older vaccine recipients (20% after dose 1; 38% after dose 2), and placebo recipients were less likely (10 to 14%) than vaccine recipients to use the medications, regardless of age or dose. Systemic events including fever and chills were observed within the first 1 to 2 days after vaccination and resolved shortly thereafter.
  
  Daily use of the electronic diary ranged from 90 to 93% for each day after the first dose and from 75 to 83% for each day after the second dose. No difference was noted between the BNT162b2 group and the placebo group.
  
  ADVERSE EVENTS
  Adverse event analyses are provided for all enrolled 43,252 participants, with variable follow-up time after dose 1 (Table S3). More BNT162b2 recipients than placebo recipients reported any adverse event (27% and 12%, respectively) or a related adverse event (21% and 5%). This distribution largely reflects the inclusion of transient reactogenicity events, which were reported as adverse events more commonly by vaccine recipients than by placebo recipients. Sixty-four vaccine recipients (0.3%) and 6 placebo recipients (<0.1%) reported lymphadenopathy. Few participants in either group had severe adverse events, serious adverse events, or adverse events leading to withdrawal from the trial. Four related serious adverse events were reported among BNT162b2 recipients (shoulder injury related to vaccine administration, right axillary lymphadenopathy, paroxysmal ventricular arrhythmia, and right leg paresthesia). Two BNT162b2 recipients died (one from arteriosclerosis, one from cardiac arrest), as did four placebo recipients (two from unknown causes, one from hemorrhagic stroke, and one from myocardial infarction). No deaths were considered by the investigators to be related to the vaccine or placebo. No Covid-19–associated deaths were observed. No stopping rules were met during the reporting period. Safety monitoring will continue for 2 years after administration of the second dose of vaccine.
  
  EFFICACY
  Table 2.
  
  Vaccine Efficacy against Covid-19 at Least 7 days after the Second Dose.Table 3.
  
  Vaccine Efficacy Overall and by Subgroup in Participants without Evidence of Infection before 7 Days after Dose 2.Figure 3.
  
  Efficacy of BNT162b2 against Covid-19 after the First Dose.
  Among 36,523 participants who had no evidence of existing or prior SARS-CoV-2 infection, 8 cases of Covid-19 with onset at least 7 days after the second dose were observed among vaccine recipients and 162 among placebo recipients. This case split corresponds to 95.0% vaccine efficacy (95% confidence interval [CI], 90.3 to 97.6; Table 2). Among participants with and those without evidence of prior SARS CoV-2 infection, 9 cases of Covid-19 at least 7 days after the second dose were observed among vaccine recipients and 169 among placebo recipients, corresponding to 94.6% vaccine efficacy (95% CI, 89.9 to 97.3). Supplemental analyses indicated that vaccine efficacy among subgroups defined by age, sex, race, ethnicity, obesity, and presence of a coexisting condition was generally consistent with that observed in the overall population (Table 3 and Table S4). Vaccine efficacy among participants with hypertension was analyzed separately but was consistent with the other subgroup analyses (vaccine efficacy, 94.6%; 95% CI, 68.7 to 99.9; case split: BNT162b2, 2 cases; placebo, 44 cases). Figure 3 shows cases of Covid-19 or severe Covid-19 with onset at any time after the first dose (mITT population) (additional data on severe Covid-19 are available in Table S5). Between the first dose and the second dose, 39 cases in the BNT162b2 group and 82 cases in the placebo group were observed, resulting in a vaccine efficacy of 52% (95% CI, 29.5 to 68.4) during this interval and indicating early protection by the vaccine, starting as soon as 12 days after the first dose.
  
  Discussion
  A two-dose regimen of BNT162b2 (30 μg per dose, given 21 days apart) was found to be safe and 95% effective against Covid-19. The vaccine met both primary efficacy end points, with more than a 99.99% probability of a true vaccine efficacy greater than 30%. These results met our prespecified success criteria, which were to establish a probability above 98.6% of true vaccine efficacy being greater than 30%, and greatly exceeded the minimum FDA criteria for authorization.9 Although the study was not powered to definitively assess efficacy by subgroup, the point estimates of efficacy for subgroups based on age, sex, race, ethnicity, body-mass index, or the presence of an underlying condition associated with a high risk of Covid-19 complications are also high. For all analyzed subgroups in which more than 10 cases of Covid-19 occurred, the lower limit of the 95% confidence interval for efficacy was more than 30%.
  
  The cumulative incidence of Covid-19 cases over time among placebo and vaccine recipients begins to diverge by 12 days after the first dose, 7 days after the estimated median viral incubation period of 5 days,10 indicating the early onset of a partially protective effect of immunization. The study was not designed to assess the efficacy of a single-dose regimen. Nevertheless, in the interval between the first and second doses, the observed vaccine efficacy against Covid-19 was 52%, and in the first 7 days after dose 2, it was 91%, reaching full efficacy against disease with onset at least 7 days after dose 2. Of the 10 cases of severe Covid-19 that were observed after the first dose, only 1 occurred in the vaccine group. This finding is consistent with overall high efficacy against all Covid-19 cases. The severe case split provides preliminary evidence of vaccine-mediated protection against severe disease, alleviating many of the theoretical concerns over vaccine-mediated disease enhancement.11
  
  The favorable safety profile observed during phase 1 testing of BNT162b24,8 was confirmed in the phase 2/3 portion of the trial. As in phase 1, reactogenicity was generally mild or moderate, and reactions were less common and milder in older adults than in younger adults. Systemic reactogenicity was more common and severe after the second dose than after the first dose, although local reactogenicity was similar after the two doses. Severe fatigue was observed in approximately 4% of BNT162b2 recipients, which is higher than that observed in recipients of some vaccines recommended for older adults.12 This rate of severe fatigue is also lower than that observed in recipients of another approved viral vaccine for older adults.13 Overall, reactogenicity events were transient and resolved within a couple of days after onset. Lymphadenopathy, which generally resolved within 10 days, is likely to have resulted from a robust vaccine-elicited immune response. The incidence of serious adverse events was similar in the vaccine and placebo groups (0.6% and 0.5%, respectively).
  
  This trial and its preliminary report have several limitations. With approximately 19,000 participants per group in the subset of participants with a median follow-up time of 2 months after the second dose, the study has more than 83% probability of detecting at least one adverse event, if the true incidence is 0.01%, but it is not large enough to detect less common adverse events reliably. This report includes 2 months of follow-up after the second dose of vaccine for half the trial participants and up to 14 weeks’ maximum follow-up for a smaller subset. Therefore, both the occurrence of adverse events more than 2 to 3.5 months after the second dose and more comprehensive information on the duration of protection remain to be determined. Although the study was designed to follow participants for safety and efficacy for 2 years after the second dose, given the high vaccine efficacy, ethical and practical barriers prevent following placebo recipients for 2 years without offering active immunization, once the vaccine is approved by regulators and recommended by public health authorities. Assessment of long-term safety and efficacy for this vaccine will occur, but it cannot be in the context of maintaining a placebo group for the planned follow-up period of 2 years after the second dose. These data do not address whether vaccination prevents asymptomatic infection; a serologic end point that can detect a history of infection regardless of whether symptoms were present (SARS-CoV-2 N-binding antibody) will be reported later. Furthermore, given the high vaccine efficacy and the low number of vaccine breakthrough cases, potential establishment of a correlate of protection has not been feasible at the time of this report.
  
  This report does not address the prevention of Covid-19 in other populations, such as younger adolescents, children, and pregnant women. Safety and immune response data from this trial after immunization of adolescents 12 to 15 years of age will be reported subsequently, and additional studies are planned to evaluate BNT162b2 in pregnant women, children younger than 12 years, and those in special risk groups, such as immunocompromised persons. Although the vaccine can be stored for up to 5 days at standard refrigerator temperatures once ready for use, very cold temperatures are required for shipping and longer storage. The current cold storage requirement may be alleviated by ongoing stability studies and formulation optimization, which may also be described in subsequent reports.
  
  The data presented in this report have significance beyond the performance of this vaccine candidate. The results demonstrate that Covid-19 can be prevented by immunization, provide proof of concept that RNA-based vaccines are a promising new approach for protecting humans against infectious diseases, and demonstrate the speed with which an RNA-based vaccine can be developed with a sufficient investment of resources. The development of BNT162b2 was initiated on January 10, 2020, when the SARS-CoV-2 genetic sequence was released by the Chinese Center for Disease Control and Prevention and disseminated globally by the GISAID (Global Initiative on Sharing All Influenza Data) initiative. This rigorous demonstration of safety and efficacy less than 11 months later provides a practical demonstration that RNA-based vaccines, which require only viral genetic sequence information to initiate development, are a major new tool to combat pandemics and other infectious disease outbreaks. The continuous phase 1/2/3 trial design may provide a model to reduce the protracted development timelines that have delayed the availability of vaccines against other infectious diseases of medical importance. In the context of the current, still expanding pandemic, the BNT162b2 vaccine, if approved, can contribute, together with other public health measures, to reducing the devastating loss of health, life, and economic and social well-being that has resulted from the global spread of Covid-19.
  
  Supported by BioNTech and Pfizer.
  
  Disclosure forms provided by the authors are available with the full text of this article at NEJM.org.
  
  Drs. Polack and Thomas contributed equally to this article.
  
  This article was published on December 10, 2020, and updated on December 16, 2020, at NEJM.org.
  
  A data sharing statement provided by the authors is available with the full text of this article at NEJM.org.
  
  We thank all the participants who volunteered for this study; and the members of the C4591001 data and safety monitoring board for their dedication and their diligent review of the data. We also acknowledge the contributions of the C4591001 Clinical Trial Group (see the Supplementary Appendix); Tricia Newell and Emily Stackpole (ICON, North Wales, PA) for editorial support funded by Pfizer; and the following Pfizer staff: Greg Adams, Negar Aliabadi, Mohanish Anand, Fred Angulo, Ayman Ayoub, Melissa Bishop-Murphy, Mark Boaz, Christopher Bowen, Salim Bouguermouh, Donna Boyce, Sarah Burden, Andrea Cawein, Patrick Caubel, Darren Cowen, Kimberly Ann Cristall, Michael Cruz, Daniel Curcio, Gabriela Dávila, Carmel Devlin, Gokhan Duman, Niesha Foster, Maja Gacic, Luis Jodar, Stephen Kay, William Lam, Esther Ladipo, Joaquina Maria Lazaro, Marie-Pierre Hellio Le Graverand-Gastineau, Jacqueline Lowenberg, Rod MacKenzie, Robert Maroko, Jason McKinley, Tracey Mellelieu, Farheen Muzaffar, Brendan O’Neill, Jason Painter, Elizabeth Paulukonis, Allison Pfeffer, Katie Puig, Kimberly Rarrick, Balaji Prabu Raja, Christine Rainey, Kellie Lynn Richardson, Elizabeth Rogers, Melinda Rottas, Charulata Sabharwal, Vilas Satishchandran, Harpreet Seehra, Judy Sewards, Helen Smith, David Swerdlow, Elisa Harkins Tull, Sarah Tweedy, Erica Weaver, John Wegner, Jenah West, Christopher Webber, David C. Whritenour, Fae Wooding, Emily Worobetz, Xia Xu, Nita Zalavadia, Liping Zhang, the Vaccines Clinical Assay Team, the Vaccines Assay Development Team, and all the Pfizer colleagues not named here who contributed to the success of this trial. We also acknowledge the contributions of the following staff at BioNTech: Corinna Rosenbaum, Christian Miculka, Andreas Kuhn, Ferdia Bates, Paul Strecker, Ruben Rizzi, Martin Bexon, Eleni Lagkadinou, and Alexandra Kemmer-Brück; and the following staff at Polymun: Dietmar Katinger and Andreas Wagner.
  
  Author Affiliations
  From Fundacion INFANT (F.P.P.) and iTrials-Hospital Militar Central (G.P.M.), Buenos Aires; State University of New York, Upstate Medical University, Syracuse (S.J.T.), and Vaccine Research and Development, Pfizer, Pearl River (J.A., A.G., K.A.S., K.K., W.V.K., D.C., P.R.D., K.U.J., W.C.G.) — both in New York; Vaccine Research and Development, Pfizer, Hurley, United Kingdom (N.K., S.L., R.B.); Vaccine Research and Development (J.L.P., P.L.) and Worldwide Safety, Safety Surveillance and Risk Management (S.M.), Pfizer, Collegeville, PA; Associação Obras Sociais Irmã Dulce and Oswaldo Cruz Foundation, Bahia (E.D.M.), and Centro Paulista de Investigação Clinica, São Paulo (C.Z.) — both in Brazil; Global Product Development, Pfizer, Peapack, NJ (S.R.); Cincinnati Children’s Hospital, Cincinnati (R.W.F.); Johns Hopkins Bloomberg School of Public Health, Baltimore (L.L.H.); BioNTech, Mainz (ÖT., U.Ş.), and Medizentrum Essen Borbeck, Essen (A.S.) — both in Germany; Tiervlei Trial Centre, Karl Bremer Hospital, Cape Town, South Africa (H.N.); Hacettepe University, Ankara, Turkey (S.Ü.); and Worldwide Safety, Safety Surveillance and Risk Management, Pfizer, Groton, CT (D.B.T.).
  
  Address reprint requests to Dr. Absalon at Pfizer, 401 N. Middletown Rd., Pearl River, NY 10965, or at [email protected].
  
  A complete list of investigators in the C4591001 Clinical Trial Group is provided in the Supplementary Appendix, available at NEJM.org.

 

[okcBob]

Do y'all remember some time back when Bill Blowjob was president and there was some sort of push for single payer health care and Hilary was deeply involved and there was some sort of flap over involvement of drug companies etc., etc.? Maybe this Covid-19 BS is the culmination - the payoff - the coup-d-gra (Spelling?) - the end of life as we know it - a THX1138 civilization instituted - - -

Don't tell me about how too many people would have to be in on the scam to make it work. Look at Hitler.

Woody

yep, that’s probably it.

 

[_CY_]

Given your postings, I don't think you could make it through a 9th grade microbiology course.

I get it that all you know is what you search on the internet but damn son......you just dig yourself deeper in the hole with every post.


https://www.nejm.org/doi/full/10.1056/NEJMoa2035389

that's total BS and you know it.
Mr. know it all with egg on face.

the previous two articles had zero, nada, nothing to do with what you claimed.
meaning either you didn't bother to read it or flat didn't understand it, probably both. ha ha ha

no research needed .. all one had to do to read the article you posted to know you are full of BS.

 

[_CY_]

I can't help it if you didn't read what I posted, nor could understand it. Probably too many big words??

I get it though, you're not used to reading facts or real science.

https://www.nejm.org/doi/full/10.1056/NEJMoa2034577

Safety and Efficacy of the BNT162b2 mRNA Covid-19 Vaccine

more ignorance showing ... do you bother reading what you post?
a whole 60 days of feedback from an on going trial.

currently NO one in the world knows what long term side effects will be for mRNA "vaccine" gene therapy.
it's impossible for any drug only 90 days old to have passed long term trials. certainly not long enough for long term side effects to show up. hence why ALL mRNA "vaccines" are experimental gene therapy that has NOT passed FDA approval.

then factor .. currently there are NO complete SARS COV-2 genome samples for researchers to work from. only fragments are available. which is why RT PCR test are bogus to identify if anyone has C-19. Kerry Mullis the inventor of RT PCR is on record for saying this exact thing.

perhaps this is too deep for you and I'm wasting my time posting this for someone that flat don't understand this topic.

 

[CHenry]

https://covid19criticalcare.com/

I'm gonna leave this here. I'm not gonna debate anything with you guys. This is here for your information. It's up to you whether you read it or not. Believe it or not. Use it or not. Enjoy.

yep its true and I am considering taking it as a preventative but i think I am already immune.