Early CD4+ T cell responses induced by the BNT162b2 SARS-CoV-2 mRNA vaccine predict immunological memory
Jie Bai, Asako Chiba, Goh Murayama, Taiga Kuga, Yoshiyuki Yahagi, Yoko Tabe, Naoto Tamura, Sachiko Miyake
Abstract
Abstract Longitudinal studies have revealed large interindividual differences in antibody responses induced by SARS-CoV-2 mRNA vaccines. Thus, we performed a comprehensive analysis of adaptive immune responses induced by three doses of the BNT162b2 SARS-CoV-2 mRNA vaccines. The responses of spike-specific CD4 + T cells, CD8 + T cells and serum IgG, and the serum neutralization capacities induced by the two vaccines declined 6 months later. The 3 rd dose increased serum spike IgG and neutralizing capacities against the wild-type and Omicron spikes to higher levels than the 2 nd dose, and this was supported by memory B cell responses, which gradually increased after the 2 nd dose and were further enhanced by the 3 rd dose. The 3 rd dose moderately increased the frequencies of spike-specific CD4 + T cells, but the frequencies of spike-specific CD8 + T cells remained unchanged. T cells reactive against the Omicron spike were 1.3-fold fewer than those against the wild-type spike. The early responsiveness of spike-specific CD4 + T, circulating T follicular helper cells and circulating T peripheral helper cells correlated with memory B cell responses to the booster vaccination, and early spike-specific CD4 + T cell responses were also associated with spike-specific CD8 + T cell responses. These findings highlight the importance of evaluating cellular responses to optimize future vaccine strategies.