Li Hongzhao, Omange Robert W, Plummer Francis A, Luo Ma
Department of Medical Microbiology, University of Manitoba, Winnipeg, Canada.
National Microbiology Laboratory, Public Health Agency of Canada, Winnipeg, Canada.
AIDS Res Ther. 2017 Sep 12;14(1):51. doi: 10.1186/s12981-017-0174-7.
HIV preferentially infects activated CD4+ T cells and mutates rapidly. The classical vaccine approach aimed to generate broad immune responses to full HIV proteins largely failed to address the potential adverse impact of increased number of activated CD4+ T cells as viral targets. Learning from natural immunity observed in a group of HIV resistant Kenyan female sex workers, we are testing a novel vaccine approach. It focuses immune response to the highly conserved sequences surrounding the HIV protease cleavage sites (PCS) to disrupt viral maturation, while limiting excessive immune activation. Our pilot studies using nonhuman primate SIV infection models suggest that this approach is feasible and promising.
人类免疫缺陷病毒(HIV)优先感染活化的CD4+ T细胞,且变异迅速。经典的疫苗研发方法旨在对完整的HIV蛋白产生广泛的免疫反应,但在很大程度上未能解决作为病毒靶标的活化CD4+ T细胞数量增加所带来的潜在不利影响。通过研究一组对HIV具有抗性的肯尼亚女性性工作者的天然免疫情况,我们正在测试一种新型疫苗研发方法。该方法将免疫反应聚焦于HIV蛋白酶切割位点(PCS)周围的高度保守序列,以破坏病毒成熟,同时限制过度的免疫激活。我们使用非人灵长类动物猴免疫缺陷病毒(SIV)感染模型进行的初步研究表明,这种方法是可行且有前景的。