This is an unedited manuscript that has been accepted for publication. Nature Research are providing this early version of the manuscript as a service to our authors and readers. The manuscript will undergo copyediting, typesetting and a proof review before it is published in its final form. Please note that during the production process errors may be discovered which could affect the content, and all legal disclaimers apply.

Phase 1/2 study of COVID-19 RNA vaccine BNT162b1 in adults


In March 2020, the World Health Organization (WHO) declared coronavirus disease 2019 (COVID-19), which is caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2)1, a pandemic. With rapidly accumulating numbers of cases and deaths reported globally2, a vaccine is urgently needed. Here we report the available safety, tolerability and immunogenicity data from an ongoing placebo-controlled, observer-blinded dose-escalation study ( identifier NCT04368728) among 45 healthy adults (18–55 years of age), who were randomized to receive 2 doses—separated by 21 days—of 10 μg, 30 μg or 100 μg of BNT162b1. BNT162b1 is a lipid-nanoparticle-formulated, nucleoside-modified mRNA vaccine that encodes the trimerized receptor-binding domain (RBD) of the spike glycoprotein of SARS-CoV-2. Local reactions and systemic events were dose-dependent, generally mild to moderate, and transient. A second vaccination with 100 μg was not administered because of the increased reactogenicity and a lack of meaningfully increased immunogenicity after a single dose compared with the 30-μg dose. RBD-binding IgG concentrations and SARS-CoV-2 neutralizing titres in sera increased with dose level and after a second dose. Geometric mean neutralizing titres reached 1.9–4.6-fold that of a panel of COVID-19 convalescent human sera, which were obtained at least 14 days after a positive SARS-CoV-2 PCR. These results support further evaluation of this mRNA vaccine candidate.

Data availability

Upon request, and subject to review, Pfizer will provide the data that support the findings of this study. Subject to certain criteria, conditions and exceptions, Pfizer may also provide access to the related individual anonymized participant data. See for more information. These data are interim data from an ongoing study for which the database is not locked. Data have not yet been source-verified or subjected to standard quality check procedures that would occur at the time of database lock and may therefore be subject to change.


  1. 1.

    World Health Organization. WHO Director-General’s Opening Remarks at the Media Briefing on COVID-19. (2020).

  2. 2.

    Coronavirus Resource Center. COVID-19 Dashboard by the Center for Systems Science and Engineering (CSSE) at Johns Hopkins University (JHU). (Johns Hopkins University & Medicine, 2020).

  3. 3.

    World Health Organization. Coronavirus Disease 2019 (COVID-19) Situation Report 154. (2020).

  4. 4.

    Alberer, M. et al. Safety and immunogenicity of a mRNA rabies vaccine in healthy adults: an open-label, non-randomised, prospective, first-in-human phase 1 clinical trial. Lancet 390, 1511–1520 (2017).

    Google Scholar 

  5. 5.

    Feldman, R. A. et al. mRNA vaccines against H10N8 and H7N9 influenza viruses of pandemic potential are immunogenic and well tolerated in healthy adults in phase 1 randomized clinical trials. Vaccine 37, 3326–3334 (2019).

    Google Scholar 

  6. 6.

    Kranz, L. M. et al. Systemic RNA delivery to dendritic cells exploits antiviral defence for cancer immunotherapy. Nature 534, 396–401 (2016).

    Google Scholar 

  7. 7.

    Şahin, U. et al. Personalized RNA mutanome vaccines mobilize poly-specific therapeutic immunity against cancer. Nature 547, 222–226 (2017).

    Google Scholar 

  8. 8.

    Petsch, B. et al. Protective efficacy of in vitro synthesized, specific mRNA vaccines against influenza A virus infection. Nat. Biotechnol. 30, 1210–1216 (2012).

    Google Scholar 

  9. 9.

    Rauch, S., Jasny, E., Schmidt, K. E. & Petsch, B. New vaccine technologies to combat outbreak situations. Front. Immunol. 9, 1963 (2018).

    Google Scholar 

  10. 10.

    Şahin, U., Karikó, K. & Türeci, Ö. mRNA-based therapeutics—developing a new class of drugs. Nat. Rev. Drug Discov. 13, 759–780 (2014).

    Google Scholar 

  11. 11.

    Karikó, K. et al. Incorporation of pseudouridine into mRNA yields superior nonimmunogenic vector with increased translational capacity and biological stability. Mol. Ther. 16, 1833–1840 (2008).

    Google Scholar 

  12. 12.

    He, Y. et al. Receptor-binding domain of SARS-CoV spike protein induces highly potent neutralizing antibodies: implication for developing subunit vaccine. Biochem. Biophys. Res. Commun. 324, 773–781 (2004).

    Google Scholar 

  13. 13.

    Zost, S. J. et al. Rapid isolation and profiling of a diverse panel of human monoclonal antibodies targeting the SARS-CoV-2 spike protein. Nat. Med. 26, 1422–1427 (2020).

    Google Scholar 

  14. 14.

    Brouwer, P. J. M. et al. Potent neutralizing antibodies from COVID-19 patients define multiple targets of vulnerability. Science 369, 643–650 (2020).

    Google Scholar 

  15. 15.

    Güthe, S. et al. Very fast folding and association of a trimerization domain from bacteriophage T4 fibritin. J. Mol. Biol. 337, 905–915 (2004).

    Google Scholar 

  16. 16.

    Bachmann, M. F. & Zinkernagel, R. M. Neutralizing antiviral B cell responses. Annu. Rev. Immunol. 15, 235–270 (1997).

    Google Scholar 

  17. 17.

    Pardi, N. et al. Expression kinetics of nucleoside-modified mRNA delivered in lipid nanoparticles to mice by various routes. J. Control. Release 217, 345–351 (2015).

    Google Scholar 

  18. 18.

    Foster, G. R. et al. IFN-α subtypes differentially affect human T cell motility. J. Immunol. 173, 1663–1670 (2004).

    Google Scholar 

  19. 19.

    Hopkins, R. J. et al. Randomized, double-blind, placebo-controlled, safety and immunogenicity study of 4 formulations of Anthrax Vaccine Adsorbed plus CPG 7909 (AV7909) in healthy adult volunteers. Vaccine 31, 3051–3058 (2013).

    Google Scholar 

  20. 20.

    Regules, J. A. et al. A recombinant vesicular stomatitis virus Ebola vaccine. N. Engl. J. Med. 376, 330–341 (2017).

    Google Scholar 

  21. 21.

    Lai, L. et al. Emergency postexposure vaccination with vesicular stomatitis virus-vectored Ebola vaccine after needlestick. J. Am. Med. Assoc. 313, 1249–1255 (2015).

    Google Scholar 

  22. 22.

    Stokes, E. K. et al. Coronavirus disease 2019 case surveillance — United States, January 22–May 30, 2020. MMWR Morb. Mortal. Wkly. Rep. 69, 759–765 (2020).

    Google Scholar 

  23. 23.

    Şahin, U. et al. Concurrent human antibody and TH1 type T-cell responses elicited by a COVID-19 RNA vaccine. Preprint at (2020).

  24. 24.

    Xie, X. et al. An infectious cDNA clone of SARS-CoV-2. Cell Host Microbe 27, 841–848 (2020).

    Google Scholar 

  25. 25.

    Muruato, A. E. et al. A high-throughput neutralizing antibody assay for COVID-19 diagnosis and vaccine evaluation. Nat. Commun. 11, 4059 (2020).

    Google Scholar 

Download references


We thank C. Monahan and D. Gantt for writing and editorial support; H. Ma, J. Trammel and K. Challagali for statistical analysis support in the generation of this manuscript; all of the participants who volunteered for this study; A. Kottkamp, R. Herati, R. Pellet Madan, M. Olson, M. Samanovic-Golden, E. Cohen, A. Cornelius, L. Frye, H. Youn, B. Fran, K. Ballani, N. Veling, J. Erb, M. Ali, L. Zhao, S. Rettig, H. Khan, H. Lambert, K. Hu, J. Hyde, M. McArthur, J. Ortiz, R. Rapaka, L. Wadsworth, G. Cummings, T. Robinson, N. Greenberg, L. Chrisley, W. Somrajit, J. Marron, C. Thomas, K. Brooks, L. Turek, P. Farley, S. Eddington, P. Komninou, M. Reymann, K. Strauss, B. Shrestha, S. Joshi, R. Barnes, R. Sukhavasi, M. Lee, A. Kwon, T. Sharp, E. Pierce, M. Criddle, A. Cline, S. Parker, M. Dickey, K. Buschle, A. Cawein, J. L. Perez, H. Seehra, D. Tresnan, R. Maroko, H. Smith, S. Tweedy, A. Jones, G. Adams, R. Malick, E. Worobetz, E. Weaver, L. Zhang, C. Devlin, D. Boyce, E. Harkins Tull, M. Boaz, M. Cruz, C. Rosenbaum, C. Miculka, A. Kuhn, F. Bates, P. Strecker, A. Kemmer-Brück, and the Vaccines Clinical Assay Team and Vaccines Assay Development Team for their assistance during this study. Staffing services were supported in part by an NYU CTSA grant (UL1 TR001445) from the National Center for Advancing Translational Sciences, National Institutes of Health. BioNTech is the sponsor of the study. Pfizer was responsible for the design, data collection, data analysis, data interpretation and writing of the report. The corresponding authors had full access to all of the data in the study and had final responsibility for the decision to submit the data for publication. All study data were available to all authors.

Author information




K.U.J., P.R.D., W.C.G., N.K., S.L., A.G., R.B., O.T. and U.Ş. were involved in the design of the overall study and strategy. K.N., M.J.M., E.E.W., R.F. and A.R.F. provided feedback on the study design. W.K., D.C., K.A.S., K.R.T., C.F.-G. and P.-Y.S. performed the immunological analyses. M.J.M., K.N., E.E.W., R.F., A.R.F., K.E.L. and V.R. collected data as study investigators. P.L. and K.K. developed the statistical design and oversaw the data analysis. J.A., K.U.J., P.R.D. and W.C.G. drafted the initial version of the manuscript. All authors reviewed and edited the manuscript and approved the final version.

Corresponding author

Correspondence to Judith Absalon.

Ethics declarations

Competing interests

N.K., J.A., A.G., S.L., R.B., K.A.S., P.L., K.K., W.K., D.C., K.R.T., P.R.D., W.C.G. and K.U.J. are employees of Pfizer and may hold stock options. U.Ş. and Ö.T. are stock owners, management board members and employees at BioNTech and are inventors on patents and patent applications related to RNA technology. M.J.M., K.E.L., K.N., E.E.W., A.R.F., R.F. and V.R. received compensation from Pfizer for their role as study investigators. C.F.-G. and P.-Y.S. received compensation from Pfizer to perform the neutralization assay.

Additional information

Peer review information Nature thanks Barbra Richardson and the other, anonymous, reviewer(s) for their contribution to the peer review of this work.

Publisher’s note Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.

Extended data figures and tables

Extended Data Fig. 1 Post vaccination changes in lymphocyte count over time.

The following time points are shown: dose 1/day 1–3, around 1 day after dose 1; dose 1/day 6–8, around 7 days after dose 1; pre-dose 2, before dose 2; dose 2/day 6–8, around 7 days after dose 2. Symbols denote group means; circle, placebo; plus, 10 μg; cross, 30 μg; triangle, 100 μg. The box-and-whisker plots show the median (centre), first and third quartiles (lower and upper edges), and minimum and maximum values (lower and upper whiskers).

Extended Data Table 1 Demographic characteristics
Extended Data Table 2 Adverse events

Supplementary information

Supplementary Information

Redacted clinical trial protocol.

Reporting Summary

Rights and permissions

Reprints and Permissions

About this article

Verify currency and authenticity via CrossMark

Cite this article

Mulligan, M.J., Lyke, K.E., Kitchin, N. et al. Phase 1/2 study of COVID-19 RNA vaccine BNT162b1 in adults. Nature (2020).

Download citation

Further reading


By submitting a comment you agree to abide by our Terms and Community Guidelines. If you find something abusive or that does not comply with our terms or guidelines please flag it as inappropriate.


Nature Briefing

Sign up for the Nature Briefing newsletter for a daily update on COVID-19 science.

Get the most important science stories of the day, free in your inbox. Sign up for Nature Briefing