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

Area of Science:

• Immunology
• Virology
• Vaccinology

Background:

• Bivalent COVID-19 vaccines aim to broaden immune responses against SARS-CoV-2 variants.
• Previous studies suggest limitations in T-cell responses to Omicron subvariants with current vaccine formulations.

Purpose of the Study:

• To investigate T-cell responses to Omicron BA.5 spike proteins after vaccination with bivalent vaccines.
• To compare T-cell reactivity between healthy donors and people living with HIV.

Main Methods:

• Utilized the functional expansion of specific T-cells (FEST) assay.
• Assessed CD4+ T-cell responses to ancestral and Omicron BA.5 spike proteins.
• Analyzed T-cell epitope cross-reactivity and monoreactivity.

Main Results:

• Bivalent vaccines did not elicit stronger T-cell responses to Omicron BA.5 compared to monovalent vaccines.
• Most T-cell epitopes targeted were unaffected by BA.5 mutations.
• Less than 10% of spike-specific CD4+ T-cell receptors showed BA.5 monoreactivity in most participants.

Conclusions:

• Current bivalent COVID-19 vaccines do not induce substantial BA.5-monoreactive T-cell responses.
• Predominance of cross-reactive T-cells suggests limited benefit against BA.5-specific mutations.
• Further research is needed to enhance T-cell immunity against emerging SARS-CoV-2 variants.