Vaccine component BNT162b4 enhances T-cell immunity against SARS-CoV-2 variants for reduced COVID-19 disease severity CellCellPress vaccine tcell immunity covid COVID19 SARSCoV2 variants immunity disease health
By Neha MathurApr 17 2023Reviewed by Lily Ramsey, LLM In a recent article published in the Cell Journal, researchers designed a novel messenger ribonucleic acid vaccine component designated BNT162b4.
The researchers demonstrated its efficacy in preventing severe coronavirus disease 2019 during live virus challenges in hamsters, an animal model most closely resembling COVID-19 manifestations in humans. Similarly, CD4+ T cells recognize their cognate epitopes on MHC class II molecules and secrete cytokines and chemokines to promote antibody production by B cells.
So far, SAR-CoV-2 S-encoding mRNA vaccine BNT162b2 has been inducing long-lasting T-cell responses in vaccinees. Even during breakthrough infections post-vaccination, researchers of several studies confirmed a positive correlation between T-cell activation and the rate of SARS-CoV-2 clearance and, as expected, a negative correlation with the viral titers.
Notably, compared to nAb epitopes, T-cell epitopes get activated faster and are conserved across SARS-CoV-2 VOCs. Their diverse nature due to certain HLA haplotypes could serve as an additional barrier to viral evasion. Accordingly, BNT162b4 is under clinical evaluation in combination with the Omicron-BA.4/BA.5 updated bivalent version of BNT162b2.
HLA ligandomics analysis showed effective cleavage at ORF1ab epitopes nearby junctional peptides. Also, MS could not detect junctional epitopes at these sites. Further, BNT162b4 elicited robust, polyfunctional T-cell responses against three antigens in mouse models. Some possible explanations are differences in T-cell epitope abundance, preferential presentation of BNT162b2 vs. BNT162b4 epitopes, and immunodominant S-specific T cells.
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