TY - JOUR T1 - Boosting with Omicron-matched or historical mRNA vaccines increases neutralizing antibody responses and protection against B.1.1.529 infection in mice JF - bioRxiv DO - 10.1101/2022.02.07.479419 SP - 2022.02.07.479419 AU - Baoling Ying AU - Suzanne M. Scheaffer AU - Bradley Whitener AU - Chieh-Yu Liang AU - Oleksandr Dmytrenko AU - Samantha Mackin AU - Kai Wu AU - Diana Lee AU - Laura E. Avena AU - Zhenlu Chong AU - James Brett Case AU - LingZhi Ma AU - Thu Kim AU - Caralyn Sein AU - Angela Woods AU - Daniela Montes Berrueta AU - Andrea Carfi AU - Sayda M. Elbashir AU - Darin K. Edwards AU - Larissa B. Thackray AU - Michael S. Diamond Y1 - 2022/01/01 UR - http://biorxiv.org/content/early/2022/02/09/2022.02.07.479419.abstract N2 - The B.1.1.529 Omicron variant jeopardizes vaccines designed with early pandemic spike antigens. Here, we evaluated in mice the protective activity of the Moderna mRNA-1273 vaccine against B.1.1.529 before or after boosting with preclinical mRNA-1273 or mRNA-1273.529, an Omicron-matched vaccine. Whereas two doses of mRNA-1273 vaccine induced high levels of serum neutralizing antibodies against historical WA1/2020 strains, levels were lower against B.1.1.529 and associated with infection and inflammation in the lung. A primary vaccination series with mRNA-1273.529 potently neutralized B.1.1.529 but showed limited inhibition of historical or other SARS-CoV-2 variants. However, boosting with mRNA-1273 or mRNA-1273.529 vaccines increased serum neutralizing titers and protection against B.1.1.529 infection. Nonetheless, the levels of inhibitory antibodies were higher, and viral burden and cytokines in the lung were slightly lower in mice given the Omicron-matched mRNA booster. Thus, in mice, boosting with mRNA-1273 or mRNA-1273.529 enhances protection against B.1.1.529 infection with limited differences in efficacy measured.Competing Interest StatementM.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 Vir Biotechnology, Kaleido, and Emergent BioSolutions and past support from Moderna not related to these studies. K.W., D.L., L.E.A., L.M., C.H., A.W., A.C., S.E. and D.K.E. are employees of and shareholders in Moderna Inc. ER -