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

Abstract

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.

Immunogenicity of SARS-CoV-2 BNT162b2 Vaccine in People with Diabetes: A Prospective Observational Study

“…These results agree with the findings of a recent study that reported a marked boosting effect on the titer of anti-S protein RBD antibody 1 week after the second dose in people with and without DM [13]. Furthermore, in agreement with recent reports that examined humoral immune response prospectively up to 6 months post-vaccination [14,15], we found a significant decline in Abs-RBD-IgG two months after the second dose of the vaccine.…”

Accelerated waning of immunity to SARS-CoV-2 mRNA vaccines in patients with immune mediated inflammatory diseases

“…36 33 [27- 25 [23][24][25][26][27][28] 26 [22][23][24][25][26][27] 22 [24][25][26] 26 [24][25][26][27][28] 27 [24][25][26][27][28][29][30][31][32][33][34][35] 22 [21][22][23][24] 32 [26][27][28][29][30][31][32][33][34] 26 [25][26][27][28][29][30][31]…”

Omicron breakthrough infection drives cross-variant neutralization and memory B cell formation

“…Currently available vaccines are based on the ancestral Wuhan-Hu-1 strain and induce antibodies with a neutralizing capacity that exceeds the breadth elicited by infection with the Wuhan strain, or with variants of concern (VOCs) (3). However, protective titers wane over time (4)(5)(6)(7) and routine booster vaccinations are thought to be needed to trigger recall immunity and maintain efficacy against new VOCs (8)(9)(10)(11).…”