Neutralizing antibody responses elicited by SARS-CoV-2 mRNA vaccination wane over time and are boosted by breakthrough infection

The waning efficacy of SARS-CoV-2 vaccines, combined with the continued emergence of variants resistant to vaccine-induced immunity, has reignited debate over the need for booster vaccine doses. To address this, we examined the neutralizing antibody response against the spike protein of five major SARS-CoV-2 variants, D614G, Alpha (B.1.1.7), Beta (B.1.351), Delta (B.1.617.2), and Omicron (B.1.1.529), in health care workers (HCWs) vaccinated with SARS-CoV-2 mRNA vaccines. Serum samples were collected pre-vaccination, three weeks post-first vaccination, one month post-second vaccination, and six months post-second vaccination. Minimal neutralizing antibody titers were detected against Omicron pseudovirus at all four time points, including for a majority of patients who had SARS-CoV-2 breakthrough infections. Neutralizing antibody titers against all other variant spike protein-bearing pseudoviruses declined dramatically from one to six months after the second mRNA vaccine dose, although SARS-CoV-2 infection boosted vaccine responses. Additionally, mRNA-1273-vaccinated HCWs exhibited about two-fold higher neutralizing antibody titers than BNT162b2-vaccinated HCWs. Together these results demonstrate possible waning of antibody-mediated protection against SARS-CoV-2 variants that is dependent on prior infection status and the mRNA vaccine received. They also show that the Omicron variant spike protein can almost completely escape from neutralizing antibodies elicited in recipients of only two mRNA vaccine doses.