Submission history

Received: 24 August 2021

Accepted: 18 January 2022

Acknowledgments

The authors would like to thank all investigators and researchers involved in this study, including the investigators on the phase 1 clinical study, M. Albayaty (AstraZeneca) and P. ForteSoto (Parexel); other members of the AstraZeneca AZD7442 Study Group: M. Liang, R. Mu, and J. Yuan; and Y-M Ching (AstraZeneca) for coordinating the development of and critically reviewing this manuscript. The authors acknowledge the contribution of T. Suscovich and SeromYx where the in vitro Fc effector function assays were conducted, and Viroclinics Biosciences where the phase 1 clinical samples were evaluated. Medical writing support was provided by Carl V Felton, Lorna Forse, and Matthew Young, and editorial support was provided by Nicola Mountford, all of Prime Global, Knutsford, UK, supported by AstraZeneca according to Good Publication Practice guidelines.

Funding: This study was supported by AstraZeneca and the Defense Advanced Research Projects Agency (under HR011-18-3-001). J.E.C. is a recipient of the 2019 Future Insight Prize from Merck KGaA, which supported part of this work with a grant. AstraZeneca scientific personnel designed, analyzed, and reported the studies.

Author contributions: Y.-M.L., P.M.M., N.L.K., M.T.E., and M.N.P. conceptualized the study. Y.-M.L., P.M.M., R.H.A., E.J.K., N.J.B., R.H.C., A.S.H., Y.H., H.A. and A.I.R. were responsible for the methods used. A.A.A., S.D., D.J.F., K.Ren., R.R., K. Rosenthal., K.M.T., O.C., J.B., L.I.C., J.D., A.I.K., and V.P.R. contributed to the investigative approach. Y.-M.L., P.M.M., R.H.A., M.E.A., K.S., J.E.C., H.B., and M.T.E. contributed to data visualization. J.M.D. was the project administrator. Y.-M.L., R.H.A, and M.T.E. were involved in drafting the original manuscript. All authors were involved in reviewing and editing the final manuscript.

Competing interests: Y.-M.L., R.H.A., M.E.A., A.A.A., S.D., D.J.F., E.J.K., K.Ren., R.R., K.Rosenthal., K.S., K.M.T., N.J.B., J.B., L.I.C., Y.H., V.P.R., A.I.R., M.N.P., and M.T.E. are employees of and hold or may hold stock in AstraZeneca. P.M.M., O.C., J.D., H.B., and N.L.K. were employees of AstraZeneca at the time of this study. N.L.K. is currently an employee of and holds stock options of Eli Lilly. H.A., A.I.K., A.S.H., and J.M.D. have no conflicts to declare. J.E.C. has served as a consultant for Luna Biologics, is a member of the Scientific Advisory Boards of CompuVax and Meissa Vaccines; is the founder of IDBiologics; and has received sponsored research agreements from Takeda Vaccines, IDBiologics, and AstraZeneca. AstraZeneca has filed patent application #PCT/EP2021/063008 related to the work described herein. R.H.C. and J.E.C. are inventors on patent applications filed by Vanderbilt University that cover SARS-CoV-2 human antibodies (PCT/US2021/024215 and U.S. 17/212,949).

Data and materials availability: Data associated with this study are available in the main text or the supplementary materials, excluding data underlying the clinical findings. Data underlying the clinical findings described in this manuscript may be requested in accordance with AstraZeneca’s data sharing policy described at https://astrazenecagrouptrials.pharmacm.com/ST/Submission/Disclosure. AstraZeneca Group of Companies allows researchers to submit a request to access anonymized patient level clinical data, aggregate clinical or genomics data (when available), and anonymized clinical study reports through the Vivli web-based data request platform. Atomic coordinates and cryo-EM maps of the reported structures of AZD8895 (COV2-2196), AZD1061 (COV2-2130), and AZD7442 (COV2-2196 and COV2-2130) have been deposited in the Protein Data Bank under PDB ID 6M0J, 6ZOY, and 7CAK, respectively. AZD8895 and AZD1061, which together make up the AZD7442 combination, may be obtained from AstraZeneca for non-commercial internal research purposes under material transfer agreements upon request to the corresponding author, M.T.E.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 this material.