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Lasting first impression: Pre-existing immunity restricts mucosal antibody responses during Omicron breakthrough

Selva, K. J.; Ramanathan, P.; Haycroft, E. R.; Reynaldi, A.; Cromer, D.; Tan, C. W.; Wang, L.-F.; Wines, B. D.; Hogarth, P. M.; Downie, L. E.; Davis, S. K.; Purcell, R. A.; Kent, H. E.; Juno, J. A.; Wheatley, A. K.; Davenport, M. P.; Kent, S. J.; Chung, A. W.

2023-03-30 infectious diseases
10.1101/2023.03.28.23287848 medRxiv
Show abstract

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 (convalescent, vaccinated) and individuals with breakthrough Delta or Omicron BA.2 infections (vaccinated, infected). Saliva from COVID-19 recovered vaccinees displayed improved antibody neutralizing activity, Fc{gamma}R engagement and IgA compared to 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. IgG, but not IgA, responses to breakthrough COVID-19 variants were dampened and narrowed by increased pre-existing vaccine-induced immunity to the ancestral strain. Salivary antibodies delayed initiation of boosting following breakthrough COVID-19 infection, especially Omicron BA.2, however, rose rapidly thereafter. Our data highlight how pre-existing immunity shapes mucosal SARS-CoV-2-specific antibody responses and has implications for long-term protection from COVID-19.

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