TY - JOUR
T1 - Phase I/II study of COVID-19 RNA vaccine BNT162b1 in adults
AU - Mulligan, Mark J.
AU - Lyke, Kirsten E.
AU - Kitchin, Nicholas
AU - Absalon, Judith
AU - Gurtman, Alejandra
AU - Lockhart, Stephen
AU - Neuzil, Kathleen
AU - Raabe, Vanessa
AU - Bailey, Ruth
AU - Swanson, Kena A.
AU - Li, Ping
AU - Koury, Kenneth
AU - Kalina, Warren
AU - Cooper, David
AU - Fontes-Garfias, Camila
AU - Shi, Pei Yong
AU - Türeci, Özlem
AU - Tompkins, Kristin R.
AU - Walsh, Edward E.
AU - Frenck, Robert
AU - Falsey, Ann R.
AU - Dormitzer, Philip R.
AU - Gruber, William C.
AU - Şahin, Uğur
AU - Jansen, Kathrin U.
N1 - Funding Information:
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.
Publisher Copyright:
© 2020, The Author(s), under exclusive licence to Springer Nature Limited.
PY - 2020/10/22
Y1 - 2020/10/22
N2 - 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.
AB - 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.
UR - http://www.scopus.com/inward/record.url?scp=85089311448&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=85089311448&partnerID=8YFLogxK
U2 - 10.1038/s41586-020-2639-4
DO - 10.1038/s41586-020-2639-4
M3 - Article
C2 - 32785213
AN - SCOPUS:85089311448
VL - 586
SP - 589
EP - 593
JO - Nature
JF - Nature
SN - 0028-0836
IS - 7830
ER -