Establishing SARS-CoV-2 membrane protein-specific antibodies as a valuable serological target via high-content microscopy

• Type of Material: Article
• Authors: Daniel M Williams, The University of Sheffield; Hailey R Hornsby, The Sheffield Medical School; Ola M Shehata, The University of Sheffield; Rebecca Brown, The Sheffield Medical School; Marta Gallis, The Sheffield Medical School; Naomi Meardon, The Sheffield Medical School; Thomas AH Newman, The Sheffield Medical School; Megan Plowright, The Sheffield Medical School; Domen Zafred, The Sheffield Medical School; Amber SM Shun-Shion, The University of Sheffield; Anthony J Hodder, The University of Sheffield; Deepa Bliss, The University of Sheffield; Andrew Metcalfe, The University of Sheffield; James R Edgar, University of Cambridge; David Gordon, Emory University; Jon R Sayers, The Sheffield Medical School; Martin J Nicklin, The Sheffield Medical School; Miles Carroll, Nuffield Department of Medicine; Paul J Collini, The Sheffield Medical School; Stephen Brown, The University of Sheffield; Thushan I de Silva, The Sheffield Medical School; Andrew A Peden, The University of Sheffield
• Language: English
• Date: 2023-07-21
• Publisher: Elsevier
• Publication Version: Final Published Version
• Copyright Statement: © 2023 The Author(s)
• Final Published Version (URL): http://dx.doi.org/10.1016/j.isci.2023.107056
• Title of Journal or Parent Work: iScience
• Volume: 26
• Issue: 7
• Start Page: 107056
• End Page: 107056
• Keywords: Microbiology; Biological sciences; Cell biology; Immunology
• Research Categories: Health Sciences, Pathology

Abstract

The prevalence and strength of serological responses mounted toward SARS-CoV-2 proteins other than nucleocapsid (N) and spike (S), which may be of use as additional serological markers, remains underexplored. Using high-content microscopy to assess antibody responses against full-length StrepTagged SARS-CoV-2 proteins, we found that 85% (166/196) of unvaccinated individuals with RT-PCR confirmed SARS-CoV-2 infections and 74% (31/42) of individuals infected after being vaccinated developed detectable IgG against the structural protein M, which is higher than previous estimates. Compared with N antibodies, M IgG displayed a shallower time-dependent decay and greater specificity. Sensitivity for SARS-CoV-2 seroprevalence was enhanced when N and M IgG detection was combined. These findings indicate that screening for M seroconversion may be a good approach for detecting additional vaccine breakthrough infections and highlight the potential to use HCM as a rapidly deployable method to identify the most immunogenic targets of newly emergent pathogens.