mRNA-1273 or mRNA-Omicron boost in vaccinated macaques elicits comparable B cell expansion, neutralizing antibodies and protection against Omicron

SARS-CoV-2 Omicron is highly transmissible and has substantial resistance to antibody neutralization following immunization with ancestral spike-matched vaccines. It is unclear whether boosting with Omicron-specific vaccines would enhance immunity and 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 antibody titers against D614G were 4760 and 270 reciprocal ID50 at week 6 (peak) and week 41 (pre-boost), respectively, and 320 and 110 for Omicron. Two weeks after boost, titers against D614G and Omicron increased to 5360 and 2980, respectively, for mRNA-1273 and 2670 and 1930 for mRNA-Omicron. Following either boost, 70-80% of spike-specific B cells were cross-reactive against both WA1 and Omicron. Significant and equivalent control of virus replication in lower airways was observed following either boost. Therefore, an Omicron boost may not provide greater immunity or protection compared to a boost with the current mRNA-1273 vaccine. ### Competing Interest Statement 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. L.W., W.S., J.R.M., 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.C., A.D., K.S., H.A. and M.G.L. are employees of Bioqual. K.S.C, L.W. and W.S. are inventors on multiple U.S. Patent Applications entitled Anti-Coronavirus Antibodies and Methods of Use. A.C. 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.