Antibody Responses to the SARS-CoV-2 Ancestral Strain and Omicron Variants in Moderna mRNA-1273 Vaccinated Active-Duty U.S. Navy Sailors and Marines.

Omicron and its subvariants have steadily gained greater capability of immune escape compared to other variants of concern, resulting in an increased incidence of reinfections even among vaccinated individuals. We evaluated the antibody response to Omicron BA.1, BA.2, and BA.4/5 in U.S. military members vaccinated with the primary 2-dose series of Moderna mRNA-1273 in a cross-sectional study. While nearly all vaccinated participants had sustained Spike (S) IgG and neutralizing antibodies (ND50) to the ancestral strain, only 7.7% participants had detectable ND50 to Omicron BA.1 at eight months post-vaccination. The neutralizing antibody response to BA.2 and BA.5 was similarly reduced. The reduced antibody neutralization of Omicron correlated with the decreased antibody binding to the Receptor-Binding Domain. The participants' seropositivity to the nuclear protein positively correlated with ND50. Our data emphasizes the need for continuous vigilance in monitoring for emerging variants and the need to identify potential alternative targets for vaccine design.