Cellular immune responses to SARS-CoV-2 in exposed seronegative individuals

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dc.contributor.author
Norton, Natasha J.
Holder, Kayla A.
Ings, Danielle P.
Harnum, Debbie O. A.
Russell, Rodney S.
Grant, Michael D.
dc.date.accessioned
2025-02-07T15:32:35Z
dc.date.available
2025-02-07T15:32:35Z
dc.date.issued
2023-04-18
dc.description.abstract - en
Some SARS-CoV-2-exposed individuals develop immunity without overt infection. We identified 11 individuals who were negative by nucleic acid testing during prolonged close contact and with no serological diagnosis of infection. As this could reflect natural immunity, cross-reactive immunity from previous coronavirus exposure, abortive infection due to de novo immune responses, or other factors, our objective was to characterize immunity against SARS-CoV-2 in these individuals. Blood was processed into plasma and peripheral blood mononuclear cells (PBMC) and screened for IgG, IgA, and IgM antibodies (Ab) against SARS-CoV-2 and common β-coronaviruses OC43 and HKU1. Receptor blocking activity and interferon-alpha (IFN-α) in plasma were also measured. Circulating T cells against SARS-CoV-2 were enumerated and CD4+ and CD8+ T cell responses discriminated after in vitro stimulation. Exposed uninfected individuals were seronegative against SARS-CoV-2 spike (S) and selectively reactive against OC43 nucleocapsid protein (N), suggesting common β-coronavirus exposure induced Ab cross-reactive against SARS-CoV-2 N. There was no evidence of protection from circulating angiotensin-converting enzyme (ACE2) or IFN-α. Six individuals had T cell responses against SARS-CoV-2, with four involving CD4+ and CD8+ T cells. We found no evidence of protection from SARS-CoV-2 through innate immunity or immunity induced by common β-coronaviruses. Cellular immune responses against SARS-CoV-2 were associated with time since exposure, suggesting that rapid cellular responses may contain SARS-CoV-2 infection below the thresholds required for a humoral response.
dc.description.sponsorship
This work was supported by a COVID-19 rapid research funding opportunity grant (Funding Reference Number: VR1–173202) from the Canadian Institutes for Health Research awarded through the COVID Immunity Task Force to M.D.G., R.S.R. and K.A.H.
dc.identifier.doi
https://doi.org/10.3390/v15040996
dc.identifier.issn
1999-4915
dc.identifier.pubmedID
37112977
dc.identifier.uri
https://open-science.canada.ca/handle/123456789/3407
dc.language.iso
en
dc.publisher - en
MDPI
dc.rights - en
Creative Commons Attribution 4.0 International (CC BY 4.0)
dc.rights - fr
Creative Commons Attribution 4.0 International (CC BY 4.0)
dc.rights.uri - en
https://creativecommons.org/licenses/by/4.0/
dc.rights.uri - fr
https://creativecommons.org/licenses/by/4.0/deed.fr
dc.subject - en
Health
dc.subject - fr
Santé
dc.subject.en - en
Health
dc.subject.fr - fr
Santé
dc.title - en
Cellular immune responses to SARS-CoV-2 in exposed seronegative individuals
dc.type - en
Article
dc.type - fr
Article
local.acceptedmanuscript.articlenum
996
local.article.journalissue
4
local.article.journaltitle - en
Viruses
local.article.journalvolume
15
local.pagination
1-14
local.peerreview - en
Yes
local.peerreview - fr
Oui
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