SARS-CoV-2 immune homology with vaccine pathogens

Recent epidemiological studies have investigated the potential effects of childhood immunization history on COVID-19 severity. Specifically, prior exposure to Bacillus Calmette–Guérin (BCG) vaccine, oral poliovirus vaccine (OPV), or measles vaccine have been postulated to reduce COVID-19 severity – putative mechanism is via stimulation of the innate immune system to provide broader protection against non-specific pathogens. While these epidemiological results remain inconclusive, we sought to investigate the potential role of adaptive immunity via cross-reactivity between vaccine preventable diseases (VPDs) with SARS-CoV-2. We implemented a comprehensive exploration of immune homology (including sequence homology, immune epitopes, and glycosylation patterns) between SARS-CoV-2 and all pathogens with FDA-approved vaccines. Sequence homology did not reveal significant alignments of protein sequences between SARS-CoV-2 with any VPD pathogens, including BCG-related strains. We also could not identify any shared T or B cell epitopes between SARS-CoV-2 and VPD pathogens among either experimentally validated epitopes or predicted immune epitopes. For N-glycosylation (N-glyc), while sites with the same tripeptides could be found between SARS-CoV-2 and certain VPD pathogens, their glycosylation potentials and positions were different. In summary, lack of immune homology between SARS-CoV-2 and VPD pathogens suggests that childhood immunization history (i.e., BCG vaccination or others) does not provide protection from SARS-CoV-2 through adaptive cross-immunity.

近期的流行病学研究探讨了儿童免疫接种史对新型冠状病毒肺炎（COVID-19）病情严重程度的潜在影响。具体而言，已有研究提出假说：此前接种卡介苗（Bacillus Calmette–Guérin, BCG）、口服脊髓灰质炎疫苗（oral poliovirus vaccine, OPV）或麻疹疫苗，可减轻COVID-19的病情严重程度，其推测的作用机制为通过激活先天免疫系统，从而获得针对非特异性病原体的广谱保护作用。尽管此类流行病学研究结果尚未定论，本研究旨在通过探究疫苗可预防疾病（vaccine preventable diseases, VPDs）与严重急性呼吸综合征冠状病毒2型（SARS-CoV-2）之间的交叉反应，分析适应性免疫的潜在作用。本研究对SARS-CoV-2与所有拥有美国食品药品监督管理局（Food and Drug Administration, FDA）批准疫苗的病原体之间的免疫同源性（包括序列同源性、免疫表位及糖基化模式）开展了全面探究。序列同源性分析未发现SARS-CoV-2与任何疫苗可预防疾病病原体（包括卡介苗相关菌株）之间存在显著的蛋白质序列比对匹配。无论是在实验验证的免疫表位还是预测免疫表位中，本研究均未发现SARS-CoV-2与疫苗可预防疾病病原体之间存在共有T细胞或B细胞表位。针对N-糖基化（N-glycosylation, N-glyc），尽管SARS-CoV-2与部分疫苗可预防疾病病原体之间可发现拥有相同三肽序列的位点，但其糖基化潜能与位点位置均存在差异。综上，SARS-CoV-2与疫苗可预防疾病病原体之间未发现免疫同源性，这表明儿童免疫接种史（如卡介苗接种或其他疫苗接种）无法通过适应性交叉免疫为个体提供针对SARS-CoV-2的保护效力。