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Preexisting immunity restricts mucosal antibody recognition of SARS-CoV-2 and Fc profiles during breakthrough infections.
Selva, Kevin J; Ramanathan, Pradhipa; Haycroft, Ebene R; Reynaldi, Arnold; Cromer, Deborah; Tan, Chee Wah; Wang, Lin-Fa; Wines, Bruce D; Hogarth, P Mark; Downie, Laura E; Davis, Samantha K; Purcell, Ruth A; Kent, Helen E; Juno, Jennifer A; Wheatley, Adam K; Davenport, Miles P; Kent, Stephen J; Chung, Amy W.
Affiliation
  • Selva KJ; Department of Microbiology and Immunology, Peter Doherty Institute for Infection and Immunity, University of Melbourne, Melbourne, Victoria, Australia.
  • Ramanathan P; Department of Microbiology and Immunology, Peter Doherty Institute for Infection and Immunity, University of Melbourne, Melbourne, Victoria, Australia.
  • Haycroft ER; Department of Microbiology and Immunology, Peter Doherty Institute for Infection and Immunity, University of Melbourne, Melbourne, Victoria, Australia.
  • Reynaldi A; Kirby Institute, University of New South Wales, Kensington, New South Wales, Australia.
  • Cromer D; Kirby Institute, University of New South Wales, Kensington, New South Wales, Australia.
  • Tan CW; Programme in Emerging Infectious Diseases, Duke-NUS Medical School, Singapore.
  • Wang LF; Infectious Diseases Translational Research Programme, Department of Microbiology and Immunology, Yong Loo Lin School of Medicine, National University of Singapore, Singapore.
  • Wines BD; Programme in Emerging Infectious Diseases, Duke-NUS Medical School, Singapore.
  • Hogarth PM; Singhealth Duke-NUS Global Health Institute, Singapore.
  • Downie LE; Immune Therapies Laboratory, Burnet Institute, Melbourne, Victoria, Australia.
  • Davis SK; Department of Immunology and Pathology, Central Clinical School, Monash University, Melbourne, Victoria, Australia.
  • Purcell RA; Department of Clinical Pathology, University of Melbourne, Melbourne, Victoria, Australia.
  • Kent HE; Immune Therapies Laboratory, Burnet Institute, Melbourne, Victoria, Australia.
  • Juno JA; Department of Immunology and Pathology, Central Clinical School, Monash University, Melbourne, Victoria, Australia.
  • Wheatley AK; Department of Clinical Pathology, University of Melbourne, Melbourne, Victoria, Australia.
  • Davenport MP; Department of Optometry and Vision Sciences, University of Melbourne, Carlton, Victoria, Australia.
  • Kent SJ; Department of Microbiology and Immunology, Peter Doherty Institute for Infection and Immunity, University of Melbourne, Melbourne, Victoria, Australia.
  • Chung AW; Department of Microbiology and Immunology, Peter Doherty Institute for Infection and Immunity, University of Melbourne, Melbourne, Victoria, Australia.
JCI Insight ; 8(18)2023 09 22.
Article in En | MEDLINE | ID: mdl-37737263
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 (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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Full text: 1 Collection: 01-internacional Database: MEDLINE Main subject: COVID-19 Limits: Humans Language: En Journal: JCI Insight Year: 2023 Document type: Article Affiliation country:

Full text: 1 Collection: 01-internacional Database: MEDLINE Main subject: COVID-19 Limits: Humans Language: En Journal: JCI Insight Year: 2023 Document type: Article Affiliation country: