Memory CD8+ T cell diversity and B cell responses correlate with protection against SARS-CoV-2 following mRNA vaccination
Memory CD8+ T cell diversity and B cell responses correlate with protection against SARS-CoV-2 following mRNA vaccination
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DOI：
10.1038/s41590-022-01313-z
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发表时间：
2022-09-22
影响因子：
30.5
通讯作者：
Pace, Luigia
中科院分区：
文献类型：
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作者：
Brasu, Nadia;Elia, Ines;Pace, Luigia
了解SARS-CoV-2信使RNA（mRNA）疫苗的免疫反应非常有趣，主要是因为对保护机制的了解很少。在本研究中，我们纵向分析了B细胞和T细胞的记忆程序对刺突（S）蛋白衍生的祖先SARS-CoV-2（武汉-1），B.1.351（β），B.1.617.2（δ）和www.example.com（omicron）变异关注（VOC）后，免疫与基于mRNA的疫苗（辉瑞）。根据首次给药后3个月体液反应的大小，我们确定了高反应者和低反应者。与低应答者相反，高应答者的特征是增强的抗体中和活性，增加的中枢记忆T细胞频率和持久的S特异性CD8（+）T细胞应答。结合抗体滴度降低与长期特异性记忆T细胞（具有不同的多反应性）相结合，发现与低反应者随后突破VOC相关。这些结果对新疫苗的设计和加强随访的新策略具有重要意义。Pace及其同事评估了mRNA疫苗接种个体中针对SARS-COV-2的抗体滴度、B细胞和T细胞记忆应答，以表明低疫苗应答者中抗体滴度降低与独特的记忆T细胞特征相关。
Understanding immune responses to SARS-CoV-2 messenger RNA (mRNA) vaccines is of great interest, principally because of the poor knowledge about the mechanisms of protection. In the present study, we analyzed longitudinally B cell and T cell memory programs against the spike (S) protein derived from ancestral SARS-CoV-2 (Wuhan-1), B.1.351 (beta), B.1.617.2 (delta) and B.1.1.529 (omicron) variants of concern (VOCs) after immunization with an mRNA-based vaccine (Pfizer). According to the magnitude of humoral responses 3 months after the first dose, we identified high and low responders. Opposite to low responders, high responders were characterized by enhanced antibody-neutralizing activity, increased frequency of central memory T cells and durable S-specific CD8(+) T cell responses. Reduced binding antibodies titers combined with long-term specific memory T cells that had distinct polyreactive properties were found associated with subsequent breakthrough with VOCs in low responders. These results have important implications for the design of new vaccines and new strategies for booster follow-up.Pace and colleagues assessed the antibody titers, B cell and T cell memory response against SARS-COV-2 in mRNA-vaccinated individuals to show that reduced antibody titers combined with a distinctive memory T cell profile in low vaccine responders correlated with breakthrough infection.