Theoretical Biology & Bioinformatics, Utrecht University, Utrecht, Netherlands.
Immunogenetics. 2023 Jun;75(3):283-293. doi: 10.1007/s00251-023-01295-8. Epub 2023 Jan 31.
Vaccination clearly decreases coronavirus disease 2019 (COVID-19) mortality; however, they also impose selection pressure on the virus, which promotes the evolution of immune escape variants. For example, despite the high vaccination level in especially Western countries, the Omicron variant caused millions of breakthrough infections, suggesting that the highly mutated spike protein in the Omicron variant can escape antibody immunity much more efficiently than the other variants of concern (VOCs). In this study, we investigated the resistance/susceptibility of T helper cell responses that are necessary for generating efficient long-lasting antibody immunity, in several VOCs. By predicting T helper cell epitopes on the spike protein for most common HLA-DRB1 alleles worldwide, we found that although most of high frequency HLA-DRB1 alleles have several potential T helper cell epitopes, few alleles like HLA-DRB1 13:01 and 11:01 are not predicted to have any significant T helper cell responses after vaccination. Using these predictions, a population based on realistic human leukocyte antigen-II (HLA-II) frequencies were simulated to visualize the T helper cell immunity on the population level. While a small fraction of this population had alarmingly little predicted CD4 T cell epitopes, the majority had several epitopes that should be enough to generate efficient B cell responses. Moreover, we show that VOC spike mutations hardly affect T helper epitopes and mainly occur in other residues of the spike protein. These results suggest that lack of long-lasting antibody responses is not likely due to loss of T helper cell epitopes in new VOCs.
疫苗接种显然降低了 2019 年冠状病毒病（COVID-19）的死亡率；然而，它们也对病毒施加了选择压力，从而促进了免疫逃逸变异体的进化。例如，尽管特别是西方国家的疫苗接种率很高，但奥密克戎变异体还是导致了数百万例突破性感染，这表明奥密克戎变异体中高度突变的刺突蛋白比其他关注的变异体（VOC）更能有效地逃避抗体免疫。在这项研究中，我们研究了几种 VOC 中产生高效持久抗体免疫所必需的 T 辅助细胞反应的抗性/敏感性。通过预测全球最常见 HLA-DRB1 等位基因上的刺突蛋白 T 辅助细胞表位，我们发现，尽管大多数高频 HLA-DRB1 等位基因都有几个潜在的 T 辅助细胞表位，但少数等位基因，如 HLA-DRB1 13:01 和 11:01，在接种疫苗后预计不会产生任何显著的 T 辅助细胞反应。使用这些预测结果，基于现实的人类白细胞抗原-II（HLA-II）频率模拟了人群水平上的 T 辅助细胞免疫。虽然一小部分人群的预测 CD4 T 细胞表位少得惊人，但大多数人群都有几个应该足以产生高效 B 细胞反应的表位。此外，我们还表明，VOC 刺突突变几乎不会影响 T 辅助表位，并且主要发生在刺突蛋白的其他残基中。这些结果表明，缺乏持久的抗体反应不太可能是由于新 VOC 中失去了 T 辅助细胞表位。
