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

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...

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Published in:	iScience Vol. 26; no. 7; p. 107056
Main Authors:	Williams, Daniel M., Hornsby, Hailey R., Shehata, Ola M., Brown, Rebecca, Gallis, Marta, Meardon, Naomi, Newman, Thomas A.H., Plowright, Megan, Zafred, Domen, Shun-Shion, Amber S.M., Hodder, Anthony J., Bliss, Deepa, Metcalfe, Andrew, Edgar, James R., Gordon, David E., Sayers, Jon R., Nicklin, Martin J., Carroll, Miles, Collini, Paul J., Brown, Stephen, de Silva, Thushan I., Peden, Andrew A.
Format:	Journal Article
Language:	English
Published:	United States Elsevier Inc 21-07-2023 The Author(s) Elsevier
Subjects:	Biological sciences Cell biology Immunology Microbiology Cell biology Biological sciences Immunology Microbiology
Online Access:	Get full text
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Summary:	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. [Display omitted] •HCM can detect SARS-CoV-2 N and S IgG responses with high specificity and sensitivity•SARS-CoV-2 M antibodies are a third high seroprevalence marker (85% of patients with COVID-19)•Anti-M IgG often displays a shallower time-dependent decline than N IgG post infection•Screening for SARS-CoV-2 M antibodies alongside N can boost serological sensitivity Biological sciences; Immunology; Microbiology; Cell biology
Bibliography:	ObjectType-Article-1 SourceType-Scholarly Journals-1 ObjectType-Feature-2 content type line 23 Contributed equally full list of consortium members can be found in the supplementary information
ISSN:	2589-0042 2589-0042
DOI:	10.1016/j.isci.2023.107056