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Author Notes:

Robert A. Seder, Vaccine Research Center, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD 20892, USA. Email: rseder@mail.nih.gov

Daniel C. Douek, Vaccine Research Center, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD 20892, USA. Email: ddouek@mail.nih.gov

M.R., N.J.S., D.C.D., and R.A.S. designed experiments. M.G., J.I.M., K.E.F., S.F.A., B.J.F., A.P.W., D.A.W., B.C.L., C.M., N.J.-B., R.C., S.L.F., M.P., M.E., V.-V.E., N.V.M., M.M., L.M., C.C.H., B.M.N., K.W.B., C.N.M.D., J.C., D.R.F., J.-P.M.T., E.M., L.P., A.V.R., B.N., D.V., A. Cook, A.D., K.S., S.T.N., S.G., A.R.H., F.L., J.R.-T., C.G.L., S.A., M.G.L., H.A., K.S.C., M.C.N., A.B.M., M.S.S., I.N.M., M.R., N.J.S., D.C.D., and R.A.S. performed, analyzed, and/or supervised experiments. M.G., J.I.M., K.E.F., S.F.A., D.A.W., I.N.M., and D.C.D. designed figures. I.-T.T., J.T., M.N., M.B., J.W., L.W., W.S., N.A.D.-R., Y.Z., E.S.Y., K.L., S.O., S.D.S., A.S.O., C.L., D.R.H., G.-Y.C., G.S.-J., I.R., Y.-T.L., A.M., K.W., J.R.M., A. Carfi, P.D.K., and D.K.E. provided critical reagents. M.G., J.I.M., D.C.D., and R.A.S. wrote manuscript. All authors edited the manuscript and provided feedback on research.

We would like to thank G. Alvarado for experimental organization and administrative support. Ethan Tyler designed the graphical abstract. The VRC Production Program (VPP) provided the WA1 protein for the avidity assay. VPP contributors include C. Anderson, V. Bhagat, J. Burd, J. Cai, K. Carlton, W. Chuenchor, N. Clbelli, G. Dobrescu, M. Figur, J. Gall, H. Geng, D. Gowetski, K. Gulla, L. Hogan, V. Ivleva, S. Khayat, P. Lei, Y. Li, I. Loukinov, M. Mai, S. Nugent, M. Pratt, E. Reilly, E. Rosales-Zavala, E. Scheideman, A. Shaddeau, A. Thomas, S. Upadhyay, K. Vickery, A. Vinitsky, C. Wang, C. Webber, and Y. Yang.

K.S.C. is an inventor on U.S. Patent no. 10,960,070 B2 and International Patent Application no. WO/2018/081318 entitled “Prefusion Coronavirus Spike Proteins and Their Use.” K.S.C. is an inventor on U.S. Patent Application no. 62/972,886 entitled “2019-nCoV Vaccine.” A.R.H., L.W., W.S., Y.Z., E.S.Y., J.R.M., P.D.K., M.R., N.J.S., and D.C.D. are inventors on U.S. Patent Application no. 63/147,419 entitled “Antibodies Targeting the Spike Protein of Coronaviruses.” L.P., A.V.R., B.N., D.V., A. Cook, A.D., K.S., H.A., and M.G.L. are employees of Bioqual. K.S.C., L.W., W.S., and Y.Z. are inventors on multiple U.S. Patent Applications entitled “Anti-Coronavirus Antibodies and Methods of Use.” G.-Y.C., G.S.-J., I.R., Y.-T.L., A.M., K.W., A. Carfi, and D.K.E. are employees of Moderna. M.S.S. serves on the scientific board of advisors for Moderna and Ocugen. The other authors declare no competing interests.

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Research Funding:

This project has been funded in part by both the Intramural Program of the National Institute of Allergy and Infectious Diseases, National Institutes of Health, Department of Health and Human Services and under HHSN272201400004C (NIAID Centers of Excellence for Influenza Research and Surveillance, CEIRS) and NIH P51 OD011132 awarded to Emory University. This work was also supported in part by the Emory Executive Vice President for Health Affairs Synergy Fund award, COVID-Catalyst-I3 Funds from the Woodruff Health Sciences Center and Emory School of Medicine, the Pediatric Research Alliance Center for Childhood Infections and Vaccines and Children’s Healthcare of Atlanta, and Woodruff Health Sciences Center 2020 COVID-19 CURE Award.

Keywords:

  • Science & Technology
  • Life Sciences & Biomedicine
  • Biochemistry & Molecular Biology
  • Cell Biology
  • INFLUENZA
  • VARIANT
  • SPIKE
  • INFECTION
  • BCL6

mRNA-1273 or mRNA-Omicron boost in vaccinated macaques elicits similar B cell expansion, neutralizing responses, and protection from Omicron

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Journal Title:

CELL

Volume:

Volume 185, Number 9

Publisher:

, Pages 1556-+

Type of Work:

Article | Final Publisher PDF

Abstract:

SARS-CoV-2 Omicron is highly transmissible and has substantial resistance to neutralization following immunization with ancestral spike-matched vaccines. It is unclear whether boosting with Omicron-matched vaccines would enhance protection. Here, nonhuman primates that received mRNA-1273 at weeks 0 and 4 were boosted at week 41 with mRNA-1273 or mRNA-Omicron. Neutralizing titers against D614G were 4,760 and 270 reciprocal ID50 at week 6 (peak) and week 41 (preboost), respectively, and 320 and 110 for Omicron. 2 weeks after the boost, titers against D614G and Omicron increased to 5,360 and 2,980 for mRNA-1273 boost and 2,670 and 1,930 for mRNA-Omicron, respectively. Similar increases against BA.2 were observed. Following either boost, 70%–80% of spike-specific B cells were cross-reactive against WA1 and Omicron. Equivalent control of virus replication in lower airways was observed following Omicron challenge 1 month after either boost. These data show that mRNA-1273 and mRNA-Omicron elicit comparable immunity and protection shortly after the boost.
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