@article{176c1f1b4c0d45d1a4380b9cdf89a4a3,
title = "Boosting with variant-matched or historical mRNA vaccines protects against Omicron infection in mice",
abstract = "The large number of spike substitutions in Omicron lineage variants (BA.1, BA.1.1., and BA.2) could jeopardize the efficacy of SARS-CoV-2 vaccines. We evaluated in mice the protective efficacy of the Moderna mRNA-1273 vaccine against BA.1 before or after boosting. Whereas two doses of mRNA-1273 vaccine induced high levels of neutralizing antibodies against historical WA1/2020 strains, lower levels against BA.1 were associated with breakthrough infection and inflammation in the lungs. A primary vaccination series with mRNA-1273.529, an Omicron-matched vaccine, potently neutralized BA.1 but inhibited historical or other SARS-CoV-2 variants less effectively. However, boosting with either mRNA-1273 or mRNA-1273.529 vaccines increased neutralizing titers and protection against BA.1 and BA.2 infection. Nonetheless, the neutralizing antibody titers were higher, and lung viral burden and cytokines were slightly lower in mice boosted with mRNA-1273.529 and challenged with BA.1. Thus, boosting with mRNA-1273 or mRNA-1273.529 enhances protection against Omicron infection with limited differences in efficacy measured.",
keywords = "Omicron, SARS-CoV-2, antibody, booster, immunity, mRNA vaccine, mice, neutralization, pathogenesis",
author = "Baoling Ying and Scheaffer, {Suzanne M.} and Bradley Whitener and Liang, {Chieh Yu} and Oleksandr Dmytrenko and Samantha Mackin and Kai Wu and Diana Lee and Avena, {Laura E.} and Zhenlu Chong and Case, {James Brett} and Ma, {Ling Zhi} and Kim, {Thu T.M.} and Sein, {Caralyn E.} and Angela Woods and Berrueta, {Daniela Montes} and Chang, {Gwo Yu} and Guillaume Stewart-Jones and Isabella Renzi and Lai, {Yen Ting} and Agata Malinowski and Andrea Carfi and Elbashir, {Sayda M.} and Edwards, {Darin K.} and Thackray, {Larissa B.} and Diamond, {Michael S.}",
note = "Funding Information: This study was supported by the NIH ( R01 AI157155 , NIAID Centers of Excellence for Influenza Research and Response (CEIRR) contracts HHSN272201400008C , 75N93021C00014 , and 75N93019C00051 ). We thank Marciela DeGrace for help in study design, Pei-Yong Shi for the WA1/2020 strains, and Peter Halfmann and Yoshihiro Kawaoka for the BA.1 and BA.2 isolates. We acknowledge the Pulmonary Morphology Core at Washington University School of Medicine for tissue sectioning and slide imaging and thank Michael Whitt for support on VSV-based Pseudovirus production. Funding Information: This study was supported by the NIH (R01 AI157155, NIAID Centers of Excellence for Influenza Research and Response (CEIRR) contracts HHSN272201400008C, 75N93021C00014, and 75N93019C00051). We thank Marciela DeGrace for help in study design, Pei-Yong Shi for the WA1/2020 strains, and Peter Halfmann and Yoshihiro Kawaoka for the BA.1 and BA.2 isolates. We acknowledge the Pulmonary Morphology Core at Washington University School of Medicine for tissue sectioning and slide imaging and thank Michael Whitt for support on VSV-based Pseudovirus production. B.Y. and S.M.S. performed and analyzed live virus neutralization assays. B.Y. S.M.S. B.W. C.-Y.L. O.D. S.M. Z.C. and J.B.C. performed mouse experiments. B.W. and B.Y. performed and analyzed viral burden analyses. B.Y. L.M. T.T.M.K. C.E.S. and A.W. performed ELISA binding experiments and analysis. G.-Y.C. G.S.-J. I.R. and Y.-T.L. performed variant monitoring and mRNA-1273.529 variant vaccine design and quality control. A.M. enabled rapid preclinical production of mRNA-1273.529 vaccine material. K.W. D.L. D.M.B. and L.E.A. performed pseudovirus neutralization assays. A.C. S.M.E. and D.K.E. provided mRNA vaccines and helped design experiments. L.B.T. and M.S.D. designed studies and supervised the research. M.S.D. and L.B.T. wrote the initial draft, with the other authors providing editorial comments. M.S.D. is a consultant for Inbios, Vir Biotechnology, Senda Biosciences, and Carnival Corporation, and on the scientific advisory boards of Moderna and Immunome. The Diamond laboratory has received unrelated funding support in sponsored research agreements from J. Virol. Biotechnol. Kaleido, and Emergent BioSolutions and past support from Moderna not related to these studies. K.W. D.L. L.E.A. L.M. T.K. C.S. A.W. A.C. S.M.E. G.-Y.C. G.S.-J. I.R. A.M. Y.-T.L. and D.K.E. are employees of and shareholders in Moderna. Publisher Copyright: {\textcopyright} 2022 Elsevier Inc.",
year = "2022",
month = apr,
day = "28",
doi = "10.1016/j.cell.2022.03.037",
language = "English",
volume = "185",
pages = "1572--1587.e11",
journal = "Cell",
issn = "0092-8674",
number = "9",
}