SARS-CoV-2 mRNA vaccination elicits a robust and persistent T follicular helper cell response in humans.

Mudd, Philip A; Minervina, Anastasia A; Pogorelyy, Mikhail V; Turner, Jackson S; Kim, Wooseob; Kalaidina, Elizaveta; Petersen, Jan; Schmitz, Aaron J et al. · Cell · 2022

basic_science · Level V

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Abstract

SARS-CoV-2 mRNA vaccines induce robust anti-spike (S) antibody and CD4<sup>+</sup> T cell responses. It is not yet clear whether vaccine-induced follicular helper CD4<sup>+</sup> T (T<sub>FH</sub>) cell responses contribute to this outstanding immunogenicity. Using fine-needle aspiration of draining axillary lymph nodes from individuals who received the BNT162b2 mRNA vaccine, we evaluated the T cell receptor sequences and phenotype of lymph node T<sub>FH</sub>. Mining of the responding T<sub>FH</sub> T cell receptor repertoire revealed a strikingly immunodominant HLA-DPB1<sup>∗</sup>04-restricted response to S<sub>167-180</sub> in individuals with this allele, which is among the most common HLA alleles in humans. Paired blood and lymph node specimens show that while circulating S-specific T<sub>FH</sub> cells peak one week after the second immunization, S-specific T<sub>FH</sub> persist at nearly constant frequencies for at least six months. Collectively, our results underscore the key role that robust T<sub>FH</sub> cell responses play in establishing long-term immunity by this efficacious human vaccine.

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