Follow-up and comparative assessment of SARS-CoV-2 IgA, IgG,
neutralizing, and total antibody responses after BNT162b2 or mRNA-1273
heterologous booster vaccination
Abstract
Background: Priming with ChAdOx1 followed by heterologous boosting have
been considered in several countries. Nevertheless, analyses that
provide a comparison of the immunogenicity of heterologous booster in
comparison to homologous primary vaccination regimens and natural
infection are lacking. In this study, we aimed to conduct a comparative
assessment of the immunogenicity between heterologous prime-boost
vaccination using BNT162b2 or mRNA-1273 and homologous primary
vaccination regimens. Methods: We matched vaccinated naïve individuals
(VN; n=673) who had received partial vaccination (n=64), primary
vaccination (n=590), or primary series plus one mRNA vaccine
heterologous booster (n=19) with individuals with a documented primary
SARS-CoV-2 infection and no vaccination record (natural infection; NI
cohort; n=206). We measured the levels of neutralizing total antibodies
(NTAbs), total antibodies (TAbs), anti-S-RBD IgG, and anti-S1 IgA
titers. Results: Homologous primary vaccination with ChAdOx1 not only
showed less potent NTAb, TAb, anti-S-RBD IgG, and anti-S1 IgA immune
responses compared to primary-BNT162b2 or mRNA-1273 vaccination regimens
(P<0.05), but also showed ~3 fold less anti-S1
IgA response compared to infection-induced immunity (P<0.001).
Nevertheless, heterologous booster dose resulted in a significant boost
of at least ~12 folds in the immune response.
Furthermore, correlation analyses revealed that both, anti-S-RBD IgG and
anti-S1 IgA significantly contributed to virus neutralization among NI
individuals, particularly in symptomatic and pauci-symptomatic
individuals, whereas, among VN individuals, anti-S-RBD IgG was the main
contributor to virus neutralization (r > 0.90, P
< 0.001). Conclusion: The results emphasize the potential
benefit of using heterologous mRNA boosters to increase antibody levels
and neutralizing capacity.