Preexisting immunity restricts mucosal antibody recognition of SARS-CoV-2 and Fc profiles during breakthrough infections

• DOI: 10.1172/jci.insight.172470
• Publication Date: 2023-09-21T18:00:49Z
• Authors: Kevin J. Selva; Pradhipa Ramanathan; Ebene R. Haycroft; Arnold Reynaldi; Deborah Cromer; Chee Wah Tan; Lin-Fa Wang; Bruce D. Wines; P. Mark Hogarth; Laura E. Downie; Samantha K. Davis; Ruth A. Purcell; Helen E. Kent; Jennifer A. Juno; Adam K. Wheatley; Miles P. Davenport; Stephen J. Kent; Amy W. Chung
• Keywords: Mucosal Immunity; Immunoglobulin A; Humoral immunity

Understanding mucosal antibody responses from SARS-CoV-2 infection and/or vaccination is crucial to develop strategies for longer term immunity, especially against emerging viral variants. We profiled serial paired and plasma antibodies COVID-19 vaccinated only vaccinees (vaccinated, uninfected), COVID-19-recovered (recovered, vaccinated), individuals with breakthrough Delta or Omicron BA.2 infections infected). Saliva displayed improved antibody-neutralizing activity, Fcγ receptor (FcγR) engagement, IgA levels compared COVID-19-uninfected vaccinees. Furthermore, repeated mRNA boosted SARS-CoV-2-specific IgG2 IgG4 in both mucosa biofluids (saliva tears) plasma; however, these rises negatively correlated FcγR engagement plasma. IgG but not IgA, variants were dampened narrowed by increased preexisting vaccine-induced immunity the ancestral strain. Salivary delayed initiation following infection, BA.2, rose rapidly thereafter. Importantly, salivary engagements enhanced infections. Our data highlight how shapes has implications long-term protection COVID-19.