Dynamics of T-cell responses following COVID-19 mRNA vaccination and breakthrough infection in older adults
Dynamics of T-cell responses following COVID-19 mRNA vaccination and breakthrough infection in older adults
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- dc.contributor.author
- Datwani, Sneha
- Kalikawe, Rebecca
- Waterworth, Rachel
- Yaseen, Fatima
- Lapointe, Hope R.
- Barad, Evan
- DeMarco, Mari L.
- Holmes, Daniel T.
- Simons, Janet
- Montaner, Julio S.G.
- Romney, Marc G.
- Brumme, Zabrina L.
- Brockman, Mark A.
- Mwimanzi, Francis
- Liang, Richard
- Sang, Yurou
- Speckmaier, Sarah
- dc.date.accessioned
- 2024-07-15T18:04:19Z
- dc.date.available
- 2024-07-15T18:04:19Z
- dc.date.issued
- 2023-07-26
- dc.description.abstract - en
- <p>Introduction: While older adults generally mount weaker antibody responses to a primary COVID-19 vaccine series, T-cell responses remain less well characterized in this population. We compared SARS-CoV-2 spike-specific T-cell responses after two- and three-dose COVID-19 mRNA vaccination and subsequent breakthrough infection in older and younger adults.</p> <p>Methods: We quantified CD4+ and CD8+ T-cells reactive to overlapping peptides spanning the ancestral SARS-CoV-2 spike protein in 40 older adults (median age 79) and 50 younger health care workers (median age 39), all COVID-19 naive, using an activation induced marker assay. T-cell responses were further assessed in 24 participants, including 8 older adults, who subsequently experienced their first SARS-CoV-2 breakthrough infection.</p> <p>Results: A third COVID-19 mRNA vaccine dose significantly boosted spike-specific CD4+ and CD8+ T-cell frequencies to above two-dose levels in older and younger adults. T-cell frequencies did not significantly differ between older and younger adults after either dose. Multivariable analyses adjusting for sociodemographic, health and vaccine-related variables confirmed that older age was not associated with impaired cellular responses. Instead, the strongest predictors of CD4+ and CD8+ T-cell frequencies post-third-dose were their corresponding post-second-dose frequencies. Breakthrough infection significantly increased both CD4+ and CD8+ T cell frequencies, to comparable levels in older and younger adults. Exploratory analyses revealed an association between HLA-A*02:03 and higher post-vaccination CD8+ T-cell frequencies, which may be attributable to numerous strong-binding HLA-A*02:03-specific CD8+ T-cell epitopes in spike.</p> <p>Conclusion: Older adults mount robust T-cell responses to two- and three-dose COVID-19 mRNA vaccination, which are further boosted following breakthrough infection.</p>
- dc.description.sponsorship
- This work was supported by the Public Health Agency of Canada through a COVID-19 Immunology Task Force COVID-19 “Hot Spots” Award (2020-HQ-000120 to MGR, ZLB, MAB). Additional funding was received from the Canadian Institutes for Health Research (GA2-177713 and the Coronavirus Variants Rapid Response Network (FRN-175622) to MAB), the Canada Foundation for Innovation through Exceptional Opportunities Fund – COVID-19 awards (to MAB, MLD, ZLB). FM was supported by a fellowship from the CIHR Canadian HIV Trials Network. FY and EB were supported by an SFU Undergraduate Research Award. MLD and ZLB hold Scholar Awards from the Michael Smith Foundation for Health Research.
- dc.identifier.doi
- https://doi.org/10.1101/2023.07.14.23292660
- dc.identifier.uri
- https://open-science.canada.ca/handle/123456789/2688
- dc.language.iso
- en
- dc.publisher
- medRxiv
- dc.rights - en
- Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International (CC BY-NC-ND 4.0)
- dc.rights - fr
- Creative Commons Attribution - Pas d'utilisation commerciale - Pas de modification 4.0 International (CC BY-NC-ND 4.0)
- dc.rights.openaccesslevel - en
- Green
- dc.rights.openaccesslevel - fr
- Vert
- dc.rights.uri - en
- https://creativecommons.org/licenses/by-nc-nd/4.0/
- dc.rights.uri - fr
- https://creativecommons.org/licenses/by-nc-nd/4.0/deed.fr
- dc.subject - en
- Health
- Coronavirus diseases
- dc.subject - fr
- Santé
- Maladie à coronavirus
- dc.subject.en - en
- Health
- Coronavirus diseases
- dc.subject.fr - fr
- Santé
- Maladie à coronavirus
- dc.title - en
- Dynamics of T-cell responses following COVID-19 mRNA vaccination and breakthrough infection in older adults
- dc.type - en
- Submitted manuscript
- dc.type - fr
- Manuscrit soumis
- local.pagination
- 1-27
- local.peerreview - en
- No
- local.peerreview - fr
- Non
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