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 before vaccination, 3 weeks after first vaccination, 1 month after second vaccination, and 6 months after second vaccination. Minimal neutralizing antibody titers were detected against Omicron pseudovirus at all four time points, including for most patients who had SARS-CoV-2 breakthrough infections. Neutralizing antibody titers against all other variant spike protein–bearing pseudoviruses declined markedly from 1 to 6 months after the second mRNA vaccine dose, although SARS-CoV-2 infection boosted vaccine responses. In addition, mRNA-1273–vaccinated HCWs exhibited about twofold 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. Waning neutralization: SARS-CoV-2 mRNA vaccines elicit robust neutralizing antibody responses, particularly against earlier strains of the virus. However, the extent to which immunity wanes over time, and the effect that waning has on responses to newer variants of concern, is still under investigation. Here, Evans et al. tested serum samples isolated from health care workers before and at three time points after vaccination. The authors observed that immunity waned by 6 months after vaccination, including against the Alpha, Beta, and Delta variants. Minimal neutralizing antibody responses to the Omicron variant were observed, regardless of sample collecting timing. Individuals who had evidence of a breakthrough infection with SARS-CoV-2 had boosted neutralizing antibody responses. Together, these data support the use of booster vaccines to ensure sustained vaccine effectiveness. [ABSTRACT FROM AUTHOR]