BNT162b2 vaccine induces neutralizing antibodies and poly-specific T cells in humans
BNT162b2 vaccine induces neutralizing antibodies and poly-specific T cells in humans
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DOI：
10.1038/s41586-021-03653-6
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发表时间：
2021-05-27
期刊：
影响因子：
64.8
通讯作者：
Tuereci, Oezlem
中科院分区：
文献类型：
--
作者：
Sahin, Ugur;Muik, Alexander;Tuereci, Oezlem
BNT 162 b2是一种核苷修饰的mRNA，配制在脂质纳米颗粒中，编码稳定在融合前构象的SARS-CoV-2刺突糖蛋白（S），已证明在预防COVID-19方面有95%的疗效（1）。在这里，我们通过提供来自健康成人（18-55岁）的额外I/II期试验的BNT 162 b2初免-加强疫苗接种诱导的免疫应答数据，扩展了先前的I/II期试验报告（2）。BNT 162 b2引发了强烈的抗体反应：加强免疫一周后，SARS-CoV-2血清几何平均50%中和滴度比从COVID-19中康复的个体的样本中观察到的滴度高出3.3倍。BNT 162 b2诱导的血清中和了22种携带不同SARS-CoV-2变体S的假病毒。大多数参与者对IFN γ（+）或IL-2（+）CD 8（+）和CD 4（+）1型辅助性T细胞有强烈的反应，在加强免疫后9周的整个观察期内均可检测到。使用肽-MHC多聚体技术，我们确定了几个BNT 162 b2诱导的表位，常见的MHC等位基因和保守的突变株。在加强免疫后一周，早期分化的效应记忆表型的表位特异性CD 8（+）T细胞占总循环CD 8（+）T细胞的0.02-2.92%，并且在八周后可检测到（0.01-0.28%）。总之，BNT 162 b2在良好耐受的剂量下针对在广泛的变体中保守的表位激发适应性体液和多特异性细胞免疫应答。
BNT162b2, a nucleoside-modified mRNA formulated in lipid nanoparticles that encodes the SARS-CoV-2 spike glycoprotein (S) stabilized in its prefusion conformation, has demonstrated 95% efficacy in preventing COVID-19(1). Here we extend a previous phase-I/II trial report(2) by presenting data on the immune response induced by BNT162b2 prime-boost vaccination from an additional phase-I/II trial in healthy adults (18-55 years old). BNT162b2 elicited strong antibody responses: at one week after the boost, SARS-CoV-2 serum geometric mean 50% neutralizing titres were up to 3.3-fold above those observed in samples from individuals who had recovered from COVID-19. Sera elicited by BNT162b2 neutralized 22 pseudoviruses bearing the S of different SARS-CoV-2 variants. Most participants had a strong response of IFN gamma(+) or IL-2(+) CD8(+) and CD4(+) T helper type 1 cells, which was detectable throughout the full observation period of nine weeks following the boost. Using peptide-MHC multimer technology, we identified several BNT162b2-induced epitopes that were presented by frequent MHC alleles and conserved in mutant strains. One week after the boost, epitope-specific CD8(+) T cells of the early-differentiated effector-memory phenotype comprised 0.02-2.92% of total circulating CD8(+) T cells and were detectable (0.01-0.28%) eight weeks later. In summary, BNT162b2 elicits an adaptive humoral and poly-specific cellular immune response against epitopes that are conserved in a broad range of variants, at well-tolerated doses.