Somogyi Eszter, Csiszovszki Zsolt, Molnár Levente, Lőrincz Orsolya, Tóth József, Pattijn Sofie, Schockaert Jana, Mazy Aurélie, Miklós István, Pántya Katalin, Páles Péter, Tőke Enikő R
Treos Bio Ltd., London, United Kingdom.
Treos Bio Zrt, Veszprém, Hungary.
Front Genet. 2021 Jun 23;12:684152. doi: 10.3389/fgene.2021.684152. eCollection 2021.
Long-term immunity to coronaviruses likely stems from T cell activity. We present here a novel approach for the selection of immunoprevalent SARS-CoV-2-derived T cell epitopes using an cohort of HLA-genotyped individuals with different ethnicities. Nine 30-mer peptides derived from the four major structural proteins of SARS-CoV-2 were selected and included in a peptide vaccine candidate to recapitulate the broad virus-specific T cell responses observed in natural infection. PolyPEPI-SCoV-2-specific, polyfunctional CD8 and CD4 T cells were detected in each of the 17 asymptomatic/mild COVID-19 convalescents' blood against on average seven different vaccine peptides. Furthermore, convalescents' complete HLA-genotype predicted their T cell responses to SARS-CoV-2-derived peptides with 84% accuracy. Computational extrapolation of this relationship to a cohort of 16,000 HLA-genotyped individuals with 16 different ethnicities suggest that PolyPEPI-SCoV-2 vaccination will likely elicit multi-antigenic T cell responses in 98% of individuals, independent of ethnicity. PolyPEPI-SCoV-2 administered with Montanide ISA 51 VG generated robust, Th1-biased CD8, and CD4 T cell responses against all represented proteins, as well as binding antibodies upon subcutaneous injection into BALB/c and hCD34 transgenic mice modeling human immune system. These results have implications for the development of global, highly immunogenic, T cell-focused vaccines against various pathogens and diseases.
对冠状病毒的长期免疫力可能源于T细胞活性。我们在此展示了一种新方法，利用一组具有不同种族背景且已进行HLA基因分型的个体来选择具有免疫普遍性的SARS-CoV-2衍生T细胞表位。从SARS-CoV-2的四种主要结构蛋白中选取了九条30聚体肽，并将其纳入一种候选肽疫苗中，以重现自然感染中观察到的广泛的病毒特异性T细胞反应。在17名无症状/轻症COVID-19康复者的血液中均检测到了针对平均七种不同疫苗肽的PolyPEPI-SCoV-2特异性多功能CD8和CD4 T细胞。此外，康复者的完整HLA基因型对其对SARS-CoV-2衍生肽的T细胞反应的预测准确率达84%。将这种关系通过计算外推到一个由16000名具有16种不同种族背景且已进行HLA基因分型的个体组成的队列，结果表明，PolyPEPI-SCoV-2疫苗接种可能会在98%的个体中引发多抗原T细胞反应，且与种族无关。在皮下注射到模拟人类免疫系统的BALB/c和hCD34转基因小鼠体内后，与Montanide ISA 51 VG联合使用的PolyPEPI-SCoV-2产生了针对所有代表性蛋白的强大的、偏向Th1的CD8和CD4 T细胞反应以及结合抗体。这些结果对开发针对各种病原体和疾病的全球通用、高免疫原性、以T细胞为重点的疫苗具有重要意义。
