Journal article

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

JCI Insight | American Society for Clinical investigation | Published : 2023

Open access

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–sp..

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Grants

Awarded by Medical Research Future Fund


Awarded by NMRC Singapore


Funding Acknowledgements

We thank the participants for their time and gracious provision of samples. We thank T. Amarasena, R. Esterbauer, K. Wragg, P. Konstandopoulos, G. Gare, K. Field, H. Kelly, and A. Kelly (University of Mel- bourne) for their outstanding technical assistance. We thank G. Taiaroa, P. Kinsella, and the molecular staff at the Victorian Infectious Diseases Reference Laboratory for performing rRT-PCR. We thank Dale Godfrey, Nicholas Gherardin, and Samuel Redmond for sharing their recombinant biotinylated-ACE2 protein. This study is supported by the Medical Research Future Fund GNT 2005544 to JAJ, SJK, and AWC and GNT 2016062 to JAJ, MPD, SJK, and AWC. DC, JAJ, MPD, SJK, and AWC are supported by NHM- RC Investigator grants. The Duke-NUS team is supported by grants from NMRC Singapore (STPRG- FY19-001, COVID19RF-003, and OFLCG19May-0034) .