Epidemiological studies suggest that the Bacillus Calmette-Guerin (BCG) vaccine may have protective effects against coronavirus disease 2019 (COVID-19); and, there are now more than 15 ongoing clinical trials seeking to determine if BCG vaccination can prevent or reduce the severity of COVID-19 (1). However, the mechanism by which BCG vaccination can induce a severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) specific T cell response is unknown. Here, in silico, we identify 8 BCG derived peptides with significant sequence homology to either SARS-CoV-2 NSP3 or NSP13 derived peptides. Using an in vitro co-culture system, we show that human CD4+ and CD8+ T cells primed with a BCG derived peptide developed enhanced reactivity to its corresponding SARS-CoV-2 derived peptide. As expected, HLA differences between individuals meant that not all persons developed immunogenic responses to all 8 BCG derived peptides. Nevertheless, all of the 20 individuals that were primed with BCG derived peptides developed enhanced T cell reactivity to at least 7 of 8 SARS-CoV-2 derived peptides. These findings provide a mechanistic basis for the epidemiologic observation that BCG vaccination confers protection from COVID-19; and supports the use of BCG vaccination to induce cross-reactive SARS-CoV-2 specific T cell responses.

中文翻译：

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卡介苗疫苗衍生肽诱导SARS-CoV-2 T细胞交叉反应

流行病学研究表明，卡介苗芽孢杆菌（BCG）疫苗可能对2019年冠状病毒疾病（COVID-19）具有保护作用; 并且，目前有15项正在进行的临床试验试图确定BCG疫苗接种是否可以预防或降低COVID-19的严重性（1）。但是，BCG疫苗可诱导严重的急性呼吸综合征冠状病毒2（SARS-CoV-2）特异性T细胞应答的机制尚不清楚。在这里，在计算机上，我们确定了8个BCG衍生肽与SARS-CoV-2 NSP3或NSP13衍生肽具有明显的序列同源性。使用体外共培养系统，我们显示了由BCG衍生肽引发的人CD4 +和CD8 + T细胞对其相应的SARS-CoV-2衍生肽具有增强的反应性。不出所料 个体之间的HLA差异意味着并非所有人都能对所有8种BCG衍生肽产生免疫原性应答。然而，用BCG衍生肽引发的所有20个人均增强了对8种SARS-CoV-2衍生肽中至少7种的T细胞反应性。这些发现为流行病学观察提供了机械基础，即BCG疫苗接种可预防COVID-19。并支持使用BCG疫苗诱导交叉反应的SARS-CoV-2特异性T细胞反应。这些发现为流行病学观察提供了机械基础，即BCG疫苗接种可预防COVID-19。并支持使用BCG疫苗诱导交叉反应的SARS-CoV-2特异性T细胞反应。这些发现为流行病学观察提供了机械基础，即BCG疫苗接种可预防COVID-19。并支持使用BCG疫苗诱导交叉反应的SARS-CoV-2特异性T细胞反应。