Frontiers in immunology · 2026
Conserved CD4 T-cell responses correlate with antibody neutralization in solid organ transplant recipients after bivalent SARS-CoV-2 vaccination.
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Stavrakis Georgia, Roznik Katerina, Stoddart Laila, Johnston T Scott, Panda Snigdha, Hage Camille, Teles Aura T, Eby Yolanda, Werbel William A, Tobian Aaron A R, Milstone Aaron M, Sette Alessandro, Grifoni Alba, Karaba Andrew H, Thompson Elizabeth A, Cox Andrea L
Аннотация
INTRODUCTION: Vaccines against SARS-CoV-2 and influenza require reformulation due to viral evolution. It remains unclear how vaccination against evolving antigens influences T-cell responses and the impact of reformulation on T-cell responses to new variants in immunocompromised hosts. Solid organ transplant recipients (SOTRs) had significantly lower antibody levels following vaccination and required repeated boosting during the COVID-19 pandemic.
METHODS: With the introduction of the Omicron spike (S) to the bivalent mRNA vaccines in 2022, the relative contribution of T-cell responses cross-reactive for Omicron mutated S sequences was assessed via intracellular cytokine staining using peptide pools containing conserved or mutated S sequences.
RESULTS: S-specific CD4 T cells recognize both conserved and Omicron mutated S sequences pre- and post-bivalent vaccination, even in the absence of evidence of prior infection as detected by T-cell responses to a novel peptide pool. CD4 T-cell responses to both conserved and Omicron mutated sequences correlated with antibody pseudo-neutralization of BA.5 S. Importantly, pre-bivalent conserved S CD4 T-cell responses significantly correlated with antibody pseudo-neutralization of BA.5 S post-bivalent.
DISCUSSION: These results emphasize the importance of conserved and cross-reactive responses in vaccine immunogenicity, providing a mechanism through which repeated boosting enhances vaccine immunogenicity in SOTRs and other immunocompromised populations.
METHODS: With the introduction of the Omicron spike (S) to the bivalent mRNA vaccines in 2022, the relative contribution of T-cell responses cross-reactive for Omicron mutated S sequences was assessed via intracellular cytokine staining using peptide pools containing conserved or mutated S sequences.
RESULTS: S-specific CD4 T cells recognize both conserved and Omicron mutated S sequences pre- and post-bivalent vaccination, even in the absence of evidence of prior infection as detected by T-cell responses to a novel peptide pool. CD4 T-cell responses to both conserved and Omicron mutated sequences correlated with antibody pseudo-neutralization of BA.5 S. Importantly, pre-bivalent conserved S CD4 T-cell responses significantly correlated with antibody pseudo-neutralization of BA.5 S post-bivalent.
DISCUSSION: These results emphasize the importance of conserved and cross-reactive responses in vaccine immunogenicity, providing a mechanism through which repeated boosting enhances vaccine immunogenicity in SOTRs and other immunocompromised populations.