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

Abstract

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 (ClinicalTrials.gov 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 https://www.pfizer.com/science/clinical-trials/trial-data-and-results 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.

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Acknowledgements

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.

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Authors

Contributions

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.

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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.

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Mulligan, M.J., Lyke, K.E., Kitchin, N. et al. Phase 1/2 study of COVID-19 RNA vaccine BNT162b1 in adults. Nature (2020). https://doi.org/10.1038/s41586-020-2639-4

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