Enhanced SARS-CoV-2 IgG durability following COVID-19 mRNA booster vaccination and comparison of BNT162b2 with mRNA-1273

Abstract

Background: BNT162b2 (Pfizer/BioNTech, Comirnaty) and mRNA-1273 (Moderna, Spikevax) are messenger RNA (mRNA) vaccines that elicit antibodies against the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) spike receptor-binding domain (S-RBD) and have been approved by the US Food and Drug Administration to combat the coronavirus disease 2019 (COVID-19) pandemic. Because vaccine efficacy and antibody levels waned over time after the 2-shot primary series, the US Food and Drug Administration authorized a booster (third) dose for both mRNA vaccines to adults in the fall of 2021.

Objective: To evaluate the magnitude and durability of S-RBD immunoglobulin (Ig)G after the booster mRNA vaccine dose in comparison to the primary series. We also compared S-RBD IgG levels after BNT162b2 and mRNA-1273 boosters and explored effects of age and prior infection.

Methods: Surrounding receipt of the second and third homologous mRNA vaccine doses, adults in an employee-based cohort provided serum and completed questionnaires, including information about previous COVID-19 infection. The IgG to S-RBD was measured using an ImmunoCAP-based system. A subset of samples were assayed for IgG to SARS-CoV-2 nucleocapsid by commercial assay.

Results: There were 228 subjects who had samples collected between 7 and 150 days after their primary series vaccine and 117 subjects who had samples collected in the same time frame after their boost. Antibody levels from 7 to 31 days after the primary series and booster were similar, but S-RBD IgG was more durable over time after the boost, regardless of prior infection status. In addition, mRNA-1273 post-boost antibody levels exceeded BNT162b2 out to 5 months.

Conclusion: The COVID-19 mRNA vaccine boosters increase antibody durability, suggesting enhanced long-term clinical protection from SARS-CoV-2 infection compared with the 2-shot regimen.

Figure 1

Timeline of vaccines, blood draws, and COVID-19 infections in the vaccine cohort. The VDH-confirmed COVID-19 infections and genotyped SARS-CoV-2 variants reported by the CDC in HHS region 3 are also illustrated.^, CDC, Centers for Disease Control and Prevention; COVID-19, coronavirus disease 2019; HHS, Health and Human Services; SARS-CoV-2, severe acute respiratory syndrome coronavirus 2; VDH, Virginia Department of Health.

Figure 2

SARS-CoV-2 S-RBD IgG trajectory after 2-dose (primary series) and 3-dose (booster) COVID-19 mRNA vaccine series. (A) IgG levels in the pre-vaccine, early and late windows. (B) Regression analysis of longitudinal paired samples. Bold lines indicate regression slopes and shaded area 95% confidence intervals. COVID-19, coronavirus disease 2019; d, day; IgG, immunoglobulin G; mRNA, messenger RNA; SARS-CoV-2, severe acute respiratory syndrome coronavirus 2; S-RBD, spike receptor-binding domain.

Figure 3

The effects of infection and age on SARS-CoV-2 S-RBD IgG levels. (A) IgG levels in uninfected (Un-) as compared with those infected before (Pre-) or after (Post-) booster vaccination. (B) S-RBD IgG levels stratified by age (excluding participants with prior self-reported COVID-19 infection). COVID-19, coronavirus disease 2019; d, day; IgG, immunoglobulin G; SARS-CoV-2, severe acute respiratory syndrome coronavirus 2; S-RBD, spike receptor-binding domain.

Figure 4

Comparison SARS-CoV-2 S-RBD IgG levels by vaccine and interaction of vaccine and age. (A) S-RBD IgG stratified by BNT162b2/Pfizer-BioNTech (P) or mRNA-1273/Moderna (M) vaccine. (B) S-RBD IgG stratified by age and vaccine. (C) Linear regression of S-RBD levels in relation to age. d, day; IgG, immunoglobulin G; SARS-CoV-2, severe acute respiratory syndrome coronavirus 2; S-RBD, spike receptor-binding domain.