We developed a global peptide vaccine against SARS-CoV-2 that addresses the dual challenges of heterogeneity in the immune responses of different individuals and potential heterogeneity of the infecting virus. PolyPEPI-SCoV-2 is a polypeptide vaccine containing nine 30-mer peptides derived from all four major structural proteins of the SARS-CoV-2. Vaccine peptides were selected based on their frequency as HLA class I and class II personal epitopes (PEPIs) restricted to multiple autologous HLA alleles of individuals in an in silico cohort of 433 subjects of different ethnicities. PolyPEPI-SCoV-2 vaccine administered with Montanide ISA 51VG adjuvant generated robust, Th1-biased CD8+ and CD4+ T cell responses against all four structural proteins of the virus, as well as binding antibodies upon subcutaneous injection into BALB/c and CD34+ transgenic mice. In addition, PolyPEPI-SCoV-2-specific, polyfunctional CD8+ and CD4+ T cells were detected ex vivo in each of the 17 asymptomatic/mild COVID-19 convalescents' blood investigated, 1-5 months after symptom onset. The PolyPEPI-SCoV-2-specific T cell repertoire used for recovery from COVID-19 was extremely diverse: donors had an average of seven different peptide-specific T cells, against the SARS-CoV-2 proteins, 87% of donors had multiple targets against at least three SARS-CoV-2 proteins and 53% against all four. In addition, PEPIs determined based on the complete HLA class I genotype of the convalescent donors were validated, with 84% accuracy, to predict PEPI-specific CD8+ T cell responses measured for the individuals. Extrapolation of the above findings to a US bone marrow donor cohort of 16,000 HLA-genotyped individuals with 16 different ethnicities (n=1,000 each ethnic group) suggest that PolyPEPI-SCoV-2 vaccination in a general population will likely elicit broad, multi-antigenic CD8+ and CD4+ T cell responses in 98% of individuals, independent of ethnicity, including Black, Asian, and Minority Ethnic (BAME) cohorts.

中文翻译：

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候选肽疫苗可模仿恢复期人类天然SARS-CoV-2免疫的异质性，并在小鼠模型中诱导广泛的T细胞反应

我们开发了一种针对SARS-CoV-2的全球肽疫苗，该疫苗解决了不同个体免疫应答中异质性和感染病毒潜在异质性的双重挑战。PolyPEPI-SCoV-2是一种多肽疫苗，包含9种30-mer肽，这些肽来自SARS-CoV-2的所有四种主要结构蛋白。根据疫苗的频率选择HLA I类和II类个人抗原决定簇（PEPI），它们仅限于433个不同种族的计算机群体的个体多个自体HLA等位基因。与Montanide ISA 51VG佐剂一起使用的PolyPEPI-SCoV-2疫苗针对病毒的所有四个结构蛋白产生了有力的，以Th1偏向的CD8 +和CD4 + T细胞应答，以及皮下注射到BALB / c和CD34 +转基因小鼠中的结合抗体。此外，在症状发作后1-5个月，在所调查的17例无症状/轻度COVID-19恢复期患者血液中，分别离体检测到了PolyPEPI-SCoV-2特异性，多功能CD8 +和CD4 + T细胞。用于从COVID-19中恢复的PolyPEPI-SCoV-2特异性T细胞库非常多种多样：供体平均有7种不同的肽特异性T细胞，针对SARS-CoV-2蛋白，有87％的供体具有多种靶向至少三种SARS-CoV-2蛋白，而53％则针对全部四种。此外，以恢复期供体的完整HLA I类基因型为基础确定的PEPI以84％的准确性得到验证，以预测针对个体测量的PEPI特异性CD8 + T细胞反应。