Department of Medical Microbiology and Infectious Diseases, University of Manitoba, Winnipeg, MB, Canada.
Center for Virology and Vaccine Research, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA, United States of America.
PLoS One. 2018 Aug 28;13(8):e0202997. doi: 10.1371/journal.pone.0202997. eCollection 2018.
HIV mutates rapidly and infects CD4+ T cells, especially when they are activated. A vaccine targeting conserved, essential viral elements while limiting CD4+ T cell activation could be effective. Learning from natural immunity observed in a group of highly HIV-1 exposed seronegative Kenyan female sex workers, we are testing a novel candidate HIV vaccine targeting the 12 viral protease cleavage sites (PCSs) (the PCS vaccine), in comparison with a vaccine targeting full-length Gag and Env (the Gag/Env vaccine) in a Mauritian cynomolgus macaque/SIV model. In this study we evaluated these vaccines for induction of mucosal antibodies to SIV immunogens at the female genital tract. Bio-Plex and Western blot analyses of cervicovaginal lavage samples showed that both the PCS and Gag/Env vaccines can elicit mucosal IgG antibody responses to SIV immunogens. Significantly higher increase of anti-PCS antibodies was induced by the PCS vaccine than by the Gag/Env vaccine (p<0.0001). The effect of the mucosal antibody responses in protection from repeated low dose pathogenic SIVmac251 challenges is being evaluated.
HIV 迅速变异并感染 CD4+T 细胞,尤其是在细胞被激活时。一种针对保守、必需病毒元件的疫苗,同时限制 CD4+T 细胞的激活,可能会有效。从一组高度暴露于 HIV-1 的肯尼亚女性性工作者中观察到的天然免疫中吸取经验,我们正在用一种新型候选 HIV 疫苗来测试针对 12 个病毒蛋白酶切割位点(PCSs)(PCs 疫苗),并与针对全长 Gag 和 Env 的疫苗(Gag/Env 疫苗)在毛里求斯猕猴/SIV 模型中进行比较。在这项研究中,我们评估了这些疫苗在诱导女性生殖道黏膜对 SIV 免疫原的抗体方面的效果。生物素标记蛋白芯片和阴道灌洗液样本的 Western blot 分析显示,PCs 疫苗和 Gag/Env 疫苗都可以诱导黏膜 IgG 抗体对 SIV 免疫原的反应。PCs 疫苗诱导的抗 PCS 抗体的增加明显高于 Gag/Env 疫苗(p<0.0001)。正在评估黏膜抗体反应对防止重复低剂量致病性 SIVmac251 挑战的保护作用。