We thank the BioNTech German clinical Phase 1/2 trial (NCT04380701, EudraCT: 2020-001038-36), the German Phase 2 rollover booster trial (NCT04949490, EudraCT: 2021-002387-50) and the global clinical Phase 2 trial (NCT04380701) participants, from whom the post-immunization human sera were obtained. We thank the many colleagues at BioNTech and Pfizer who developed and produced the BNT162b2 mRNA vaccine candidate. We thank S. Jägle for logistical support, and B. Huang for support generating the overview figure S4. We thank the VisMederi team for performing excellent work on live virus-neutralizing antibody assays. We thank C. Heiser, A. Telorman, K. Krüger, C. Müller, A. Wanamaker, N. Williams and J. VanCamp for sample demographics support. Funding: This work was supported by BioNTech and Pfizer. Author contributions: U.S., Ö.T., and A.M. conceived and conceptualized the work. A.M, B.G.L., J.R., H.C., Q.Y., K.A.S and R.G planned and supervised experiments. A.M., A.W., B.G.L, J.M., J.R., M.B., N.B. and R.G. performed experiments. A.M., A.P., B.G.L., J.R., K.A.S., O.O., R.G., and S.S. and analyzed data. U.S., Ö.T., A.M., A.F., and K.A.S. interpreted data and wrote the manuscript. All authors supported the review of the manuscript. Competing interests: U.S. and Ö.T. are management board members and employees at BioNTech SE. A.F., A.M., A.W., B.G.L, J.M., J.R., M.B, N.B., O.O., S.S. and R.G. are employees at BioNTech SE. A.P. is an employee at BioNTech US. U.S., Ö.T. and A.M. are inventors on patents and patent applications related to RNA technology and COVID-19 vaccine. U.S., Ö.T., N.B., A.F., A.M., A.P., A.W., B.G.L., J.M., O.O., J.R., S.S., and R.G. have securities from BioNTech SE; H.C., Q.Y., K.A.S. are employees at Pfizer and may have securities from Pfizer. Data and materials availability: All data are available in the main manuscript or the supplementary materials. Trial participant baseline characteristics are provided in table S1. The neutralization titers are provided in tables S2 to S5. Materials are available from the authors under a material transfer agreement with BioNTech. This work is licensed under a Creative Commons Attribution 4.0 International (CC BY 4.0) license, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. To view a copy of this license, visit https://creativecommons.org/licenses/by/4.0/. This license does not apply to figures/photos/artwork or other content included in the article that is credited to a third party; obtain authorization from the rights holder before using such material.