Fc properties of SARS-CoV-2 spike-specific antibodies elicited by vaccines and infection

Abstract

Abstract Since its emergence in 2019, SARS-CoV-2 has infected millions of people and several vaccines have been approved for clinical use worldwide. Antibodies against the spike protein of SARS-CoV-2 are a critical immune determinant for protection against this virus. While virus neutralization is a key function of spike-specific antibodies, antibodies also mediate Fc-dependent activities that can play a role in protection or pathogenesis. This study compared the Fc properties and functions of anti-spike antibodies elicited by Pfizer/BioNtech or Moderna mRNA vaccines, Sputnik rAd26+rAd5 vaccines, or natural SARS-CoV-2 infection. We first examined immunoglobulin (Ig) isotypes in sera or plasma from the three groups. IgG1 antibodies against the spike protein were the predominant isotype, produced to high levels by the vast majority of the subjects in the three groups. In addition to IgG1, the mRNA vaccines also elicited IgM, IgG2-4, and IgA1-2, whereas the Sputnik vaccines induced only IgG4. Convalescent COVID-19 patients had yet a distinct set of isotypes, displaying mainly IgM and IgA1 alongside IgG1. When we examined antibody functions, spike-specific antibodies from both mRNA and Sputnik vaccine groups showed greater capacities to bind and activate complement than those from the convalescent COVID-19 patients. However, the Sputnik vaccine-induced antibodies had a greater potency of binding the ADCC-activating FcγRIIIa receptor, although the Sputnik vaccines induced lower Ig levels against spike than the mRNA vaccines. These data demonstrate that antibodies with distinct Ig isotypes/subtypes and Fc functions were elicited by different COVID-19 vaccines and by natural SARS-CoV-2 infection. This work was supported in part by the Department of Veterans Affairs [Merit Review Grant I01BX005794] (C.E.H.) and [Research Career Scientist Award 1IK6BX004607] (C.E.H.); the National Institutes of Health [grant AI139290] to C.E.H., [grants R01 AI123449, R21 AI1498033] to B.L, the Department of Medicine of the Icahn School of Medicine at Mount Sinai (C.E.H.); the Department of Microbiology and the Ward-Coleman estate for endowing the Ward-Coleman Chairs at the Icahn School of Medicine at Mount Sinai (B.L.), and institutional funding as well as anonymous philanthropic donations (V.S.).