Max Rady College of Medicine, University of Manitoba, Winnipeg, Manitoba, Canada.
Biochemistry & Medical Genetics, University of Manitoba, Winnipeg, Manitoba, Canada; National Microbiology Laboratory, Winnipeg, Manitoba, Canada.
Vaccine. 2021 May 6;39(19):2676-2683. doi: 10.1016/j.vaccine.2021.03.068. Epub 2021 Apr 15.
Development of an effective HIV-1 vaccine has been a great challenge faced by the research community. Recently a novel strategy targeting the viral protease cleavage sites (PCSs) has been tested and shown promising results. This T cell-based vaccine strategy depends on individuals expressing certain HLA class I molecules and since each population has unique distributions of HLA class I alleles, population coverage analysis is required to assess feasibility. Utilizing the validated CD8 T cell epitope data from previous studies we conducted coverage analysis of an HIV-1 vaccine targeting the sequences surrounding all 12-PCSs, Gag-PCSs, and Pol-PCSs. The population coverage, average epitope hit, and minimum number of epitopes recognized by 90% of the population (PC90) was compiled for 66 countries and 16 geographical regions using the web tool provided by "Immune Epitope Database and Analysis Resource". Our analysis shows that the coverage for an HIV-1 vaccine targeting sequences surrounding all 12 PCSs, 5 PCSs in Gag or 6 PCSs in Pol can cover ~ 70% to ~ 100% of the populations analyzed. There was no statistical difference in population coverages for the majority of populations examined when comparing the CD8 T cell epitope sets (12-PCSs, Gag-PCSs, and Pol-PCSs). As expected, vaccines targeting more sequences will have more CD8 T cell epitopes, as the mean average epitope hit for the 12-PCSs, Gag-PCSs, and Pol-PCSs across all countries studied was 9.45, 4.76, and 4.74, respectively, and across all geographical regions was 9.76, 4.99, and 4.92, respectively. The average PC90 for the 12-PCSs, Gag-PCSs, and Pol-PCSs across all countries studied was 2.53, 1.31, and 1.41, respectively, and across all geographical regions was 2.24, 1.23, and 1.29, respectively. Thus, vaccines targeting sequences surrounding the HIV-1 PCSs can cover broad populations; however, whether targeting a subset of the PCSs is sufficient to prevent acquisition requires further preclinical investigation.
开发有效的 HIV-1 疫苗一直是研究界面临的巨大挑战。最近，一种针对病毒蛋白酶切割位点（PCSs）的新策略已经过测试，并显示出有希望的结果。这种基于 T 细胞的疫苗策略取决于个体表达某些 HLA Ⅰ类分子，由于每个人群的 HLA Ⅰ类等位基因分布独特，因此需要进行人群覆盖分析以评估可行性。利用以前研究中经过验证的 CD8 T 细胞表位数据，我们对针对所有 12-PCSs、Gag-PCSs 和 Pol-PCSs 周围序列的 HIV-1 疫苗进行了覆盖分析。使用“免疫表位数据库和分析资源”提供的网络工具，为 66 个国家和 16 个地理区域编译了针对所有 12 PCSs、Gag 中的 5 PCSs 或 Pol 中的 6 PCSs 的 HIV-1 疫苗的人群覆盖率、平均表位命中数和 90%人群识别的最小表位数（PC90）。我们的分析表明，针对所有 12 PCSs 周围序列、Gag 中的 5 PCSs 或 Pol 中的 6 PCSs 的 HIV-1 疫苗的覆盖范围可以覆盖70%至100%分析的人群。在大多数人群中，比较 CD8 T 细胞表位集（12-PCSs、Gag-PCSs 和 Pol-PCSs）时，人群覆盖率没有统计学差异。正如预期的那样，针对更多序列的疫苗将具有更多的 CD8 T 细胞表位，因为针对所有研究国家的 12-PCSs、Gag-PCSs 和 Pol-PCSs 的平均平均表位命中数分别为 9.45、4.76 和 4.74，针对所有地理区域的平均平均表位命中数分别为 9.76、4.99 和 4.92。针对所有研究国家的 12-PCSs、Gag-PCSs 和 Pol-PCSs 的平均 PC90 分别为 2.53、1.31 和 1.41，针对所有地理区域的平均 PC90 分别为 2.24、1.23 和 1.29。因此，针对 HIV-1 PCSs 周围序列的疫苗可以覆盖广泛的人群；然而，针对 PCSs 的子集是否足以预防获得还需要进一步的临床前研究。
