JCI Insight (Sep 2023)

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

  • 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

Journal volume & issue
Vol. 8, no. 18

Abstract

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

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