Comparative 6-Month Wild-Type and Delta-Variant Antibody Levels and Surrogate Neutralization for Adults Vaccinated with BNT162b2 versus mRNA-1273

Abstract

While mRNA vaccines are highly efficacious against short-term COVID-19, long-term immunogenicity is less clear. We compared humoral immunogenicity between BNT162b2 and mRNA-1273 vaccines 6 months after the first vaccine dose, examining the wild-type strain and multiple Delta-variant lineages. Using samples from a prospective observational cohort study of adult paramedics, we included COVID-19-negative participants who received two BNT162b2 or mRNA-1273 vaccines, and provided a blood sample 170 to 190 days post first vaccine dose. We compared wild-type spike IgG concentrations using the Mann-Whitney U test. We also compared secondary outcomes of: receptor binding domain (RBD) wild-type antibody concentrations, and inhibition of angiotensin-converting enzyme 2 (ACE-2) binding to spike proteins from the wild-type strain and five Delta-variant lineages. We included 571 adults: 475 BNT162b2 (83%) and 96 mRNA-1273 (17%) vaccinees, with a mean age of 39 (SD = 10) and 43 (SD = 10) years, respectively. Spike IgG antibody concentrations were significantly higher (P < 0.0001) for those who received mRNA-1273 (GM 601 BAU/mL [GSD 2.05]) versus BNT162b2 (GM 375 BAU/mL [GSD 2.33) vaccines. Results of RBD antibody comparisons (P < 0.0001), and inhibition of ACE-2 binding to the wild-type strain and all tested Delta lineages (all P < 0.0001), were consistent. Adults who received two doses of mRNA-1273 vaccines demonstrated improved wild-type and Delta variant-specific humoral immunity outcomes at 6 months compared with those who received two doses of the BNT162b2 vaccine. IMPORTANCE The BNT162b2 and mRNA-1273 mRNA SARS-CoV-2 vaccines have demonstrated high efficacy for preventing short-term COVID-19. However, comparative long-term effectiveness is unclear, especially pertaining to the Delta variant. We tested virus-specific antibody responses 6 months after the first vaccine dose and compared individuals who received the BNT162b2 and mRNA-1273 SARS-CoV-2 vaccines. We found that individuals who received the mRNA-1273 vaccine demonstrated superior serological markers at 6 months in comparison with those who received the BNT162b2 vaccine.

Keywords: COVID-19; Delta; SARS-CoV-2; spike.

FIG 1

Comparison of spike and receptor-binding domain antibody concentrations (BAU/mL), stratified by mRNA vaccine type. (A) Spike IgG antibody concentrations (BAU/mL), measured on the V-PLEX assay. (B) Receptor-binding domain (RBD) IgG antibody concentrations (BAU/mL), measured on the V-PLEX assay. (C) Spike total antibody concentrations (BAU/mL), measured on the Elecsys assay. The black line represents the geometric mean. P values derived from the Mann-Whitney U test. BAU/mL, binding antibody units per mL.

FIG 2

Comparison of inhibition of ACE-2 binding to Delta variant and wild-type strain spike protein concentrations (U/mL), stratified by mRNA vaccine type. Delta variant spike proteins: A. AY.1.; B. AY.2.; C. B.1.617.2/AY.3/AY.5/AY.6/AY.7/AY.14; D. B.1.617.2/AY.4.; E. AY.12. Wild-Type Spike Protein results in Panel F. The black line represents the geometric mean. P values derived from the Mann-Whitney U test. U/mL, units per mL.