Abstract

Antibodies (Abs) are essential for the host immune response against SARS-CoV-2, and all the vaccines developed so far have been designed to induce Abs targeting the SARS-CoV-2 spike. Many studies have examined Ab responses in the blood from vaccinated and infected individuals. However, since SARS-CoV-2 is a respiratory virus, it is also critical to understand the mucosal Ab responses at the sites of initial virus exposure. Here, we examined plasma versus saliva Ab responses in vaccinated and convalescent patients. Although saliva levels were significantly lower, a strong correlation was observed between plasma and saliva total Ig levels against all SARS-CoV-2 antigens tested. Virus-specific IgG1 responses predominated in both saliva and plasma, while a lower prevalence of IgM and IgA1 Abs was observed in saliva. Antiviral activities of plasma Abs were also studied. Neutralization titers against the initial WA1 (D614G), B.1.1.7 (alpha) and B.1.617.2 (delta) strains were similar but lower against the B.1.351 (beta) strain. Spike-specific antibody-dependent cellular phagocytosis (ADCP) activities were also detected and the levels correlated with spike-binding Ig titers. Interestingly, while neutralization and ADCP potencies of vaccinated and convalescent groups were comparable, enhanced complement deposition to spike-specific Abs was noted in vaccinated versus convalescent groups and corresponded with higher levels of IgG1 plus IgG3 among the vaccinated individuals. Altogether, this study demonstrates the detection of Ab responses after vaccination or infection in plasma and saliva that correlate significantly, although Ig isotypic differences were noted. The induced plasma Abs displayed Fab-mediated and Fc-dependent functions with comparable neutralization and ADCP potencies, but a greater capacity to activate complement was elicited upon vaccination.

Highlights

  • Antibodies (Abs) are an essential component of the immune responses against coronavirus disease-2019 (COVID-19)

  • Plasma and saliva samples were titrated for total Ig against SARS-CoV-2 spike, receptor-binding domain (RBD), S1, S2, and nucleoprotein antigens

  • This study provides evidence that plasma and saliva levels of Abs elicited after vaccination or infection correlate strongly

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Summary

Introduction

Antibodies (Abs) are an essential component of the immune responses against coronavirus disease-2019 (COVID-19). Many studies have evaluated Ab responses against SARS-CoV-2 elicited by infection or vaccination, but most examined Abs in the blood. IgA is the major Ab isotype of the mucosal immune system and exists as IgA1 and IgA2 [8] Of these two subtypes, IgA1 Abs predominate in both serum and secretions, but IgA2 percentages are higher in secretions than in serum. IgA1 Abs predominate in both serum and secretions, but IgA2 percentages are higher in secretions than in serum Consistent with this information, our previous study demonstrated that anti-spike Ab responses in convalescent plasma collected 1-2 months post-infection, were dominated by IgG1, the levels varied tremendously among subjects [9]. The isotypes of vaccine-elicited Ab responses in mucosa have not been studied so far

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