Identification of cross reactive T cell responses in adenovirus based COVID 19 vaccines

Gardner, Joshua, Abrams, Simon Timothy, Toh, Cheng-Hock, Parker, Alan L. ORCID: https://orcid.org/0000-0002-9302-1761, Lovatt, Charlotte, Nicolson, Phillip L. R., Watson, Steve P., Grice, Sophie, Hering, Luisa, Pirmohamed, Munir and Naisbitt, Dean J. 2024. Identification of cross reactive T cell responses in adenovirus based COVID 19 vaccines. npj Vaccines 9 (1) , 99. 10.1038/s41541-024-00895-z

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Abstract

Vaccination has proven to be a valuable tool to combat SARS-CoV-2. However, reports of rare adverse reactions such as thrombosis/thrombocytopenia syndrome after ChAdOx1 nCoV-19 vaccination have caused scientific, public and media concern. ChAdOx1 was vectorised from the Y25 chimpanzee adenovirus, which was selected due to low human seroprevalence to circumvent pre-existing immunity. In this study, we aimed to explore patterns of T-cell activation after SARS-CoV-2 COVID-19 vaccine exposure in vitro using PBMCs collected from pre-pandemic ChAdOx1 nCoV-19 naïve healthy donors (HDs), and ChAdOx1 nCoV-19 and Pfizer vaccinated controls. PBMCs were assessed for T-cell proliferation using the lymphocyte transformation test (LTT) following exposure to SARS-CoV-2 COVID-19 vaccines. Cytokine analysis was performed via intracellular cytokine staining, ELISpot assay and LEGENDplex immunoassays. T-cell assays performed in pre-pandemic vaccine naïve HDs, revealed widespread lymphocyte stimulation after exposure to ChAdOx1 nCoV-19 (95%), ChAdOx-spike (90%) and the Ad26.COV2. S vaccine, but not on exposure to the BNT162b2 vaccine. ICS analysis demonstrated that CD4+ CD45RO+ memory T-cells are activated by ChAdOx1 nCoV-19 in vaccine naïve HDs. Cytometric immunoassays showed ChAdOx1 nCoV-19 exposure was associated with the release of proinflammatory and cytotoxic molecules, such as IFN-γ, IL-6, perforin, granzyme B and FasL. These studies demonstrate a ubiquitous T-cell response to ChAdOx1 nCoV-19 and Ad26.COV2. S in HDs recruited prior to the SARS-CoV-2 pandemic, with T-cell stimulation also identified in vaccinated controls. This may be due to underlying T-cell cross-reactivity with prevalent human adenoviruses and further study will be needed to identify T-cell epitopes involved.

Item Type:	Article
Date Type:	Published Online
Status:	Published
Schools:	Medicine
Publisher:	Nature Research
ISSN:	2059-0105
Funders:	NIHR
Date of First Compliant Deposit:	6 June 2024
Date of Acceptance:	28 May 2024
Last Modified:	20 Jun 2024 09:00
URI:	https://orca.cardiff.ac.uk/id/eprint/169505

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