Bivalent mRNA COVID vaccines elicit predominantly cross-reactive CD4+ T cell clonotypes

• Published in: Cell reports. Medicine Vol. 5; no. 3; p. 101442
• Main Authors: Sop, Joel, Traut, Caroline C., Dykema, Arbor G., Hunt, Joanne H., Beckey, Tyler P., Basseth, Christie R., Antar, Annukka A.R., Laeyendecker, Oliver, Smith, Kellie N., Blankson, Joel N.
• Format: Journal Article
• Language: English
• Published: United States Elsevier Inc 19-03-2024; Elsevier
• Subjects: BA.5; bivalent vaccine; CD4-Positive T-Lymphocytes; COVID-19 - prevention & control; COVID-19 Vaccines; Humans; mRNA Vaccines; RNA, Messenger - genetics; SARS-CoV-2; Spike Glycoprotein, Coronavirus - genetics; T cell receptor; T-Lymphocytes; BA.5; bivalent vaccine; SARS-CoV-2; T cell receptor
• ISSN: 2666-3791; 2666-3791
• DOI: 10.1016/j.xcrm.2024.101442

Bivalent COVID vaccines containing mRNA for ancestral and Omicron BA.5 spike proteins do not induce stronger T cell responses to Omicron BA.5 spike proteins than monovalent vaccines that contain only ancestral spike mRNA. The reasons for this finding have not been elucidated. Here, we show that healthy donors (HDs) and people living with HIV (PLWH) on antiretroviral therapy mostly target T cell epitopes that are not affected by BA.5 mutations. We use the functional expansion of specific T cells (FEST) assay to determine the percentage of CD4+ T cells that cross-recognize both spike proteins and those that are monoreactive for each protein. We show a predominance of cross-reactive CD4+ T cells; less than 10% percent of spike-specific CD4+ T cell receptors were BA.5 monoreactive in most HDs and PLWH. Our data suggest that the current bivalent vaccines do not induce robust BA.5-monoreactive T cell responses.
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•Bivalent vaccines induce similar T cell responses to ancestral and BA.5 spike•People living with HIV have similar T cell responses to healthy donors•Most spike-specific T cells cross-recognize ancestral and BA.5 spike proteins•T cells mostly recognize epitopes that are not affected by BA.5 mutations
Sop et al. analyze T cell responses induced by ancestral spike/BA.5 spike bivalent mRNA COVID vaccines. They demonstrate that in healthy donors and people living with HIV, most spike-specific T cells cross-recognize ancestral and BA.5 spike proteins and few BA.5 spike monoreactive T cells are induced.