Development of a Vaccine for HIVAIDS: Cellular Immunity

我们的HIV疫苗方法是基于用复制型腺病毒进行初始免疫 (Ad)携带HIV基因的载体，然后用HIV包膜进行加强免疫 蛋白Ad-HIV疫苗在粘膜诱导位点的上皮细胞中复制， 从而在粘膜效应部位以及在 血我们已经证明，最初的免疫接种Ad-HIV疫苗也会刺激 产生抗HIV抗体。总之，该方案诱导了强大而持久的保护作用， 应答我们已经证明，在上呼吸道接种Ad-HIV疫苗 道以及肠道（通过口服免疫）激发具有“归巢”功能的记忆性T细胞。 受体”导致它们运输到肠道，这是HIV感染的主要部位。因此 疫苗方法增强了对预防或治疗的关键部位的细胞免疫， 控制艾滋病毒感染。HIV DNA联合疫苗的研究 联合细胞因子佐剂的疫苗，然后是Ad-HIV疫苗和包膜蛋白 加强免疫显示它们具有免疫原性。该研究强调了几个可以 优化了对HIV感染的更大保护效力。临床前研究， 食蟹猴的起源，确定了MHC I类单倍型与 对猴免疫缺陷病毒（SIV）-HIV嵌合体攻击的天然保护 病毒（SHIV）。这些结果将使在这种动物模型中更好地设计疫苗研究成为可能。 此外，对这种自然宿主防御机制的研究可能会提出新的途径， 用于预防艾滋病毒战略。

Our HIV vaccine approach is based on initial immunization with a replicating adenovirus (Ad) vector carrying an HIV gene(s) followed by a booster immunization with an HIV envelope protein. The Ad-HIV vaccine replicates in epithelial cells that line mucosal inductive sites, thus eliciting strong, persistent cellular immunity at mucosal effector sites as well as in the blood. We have shown that initial immunizations with an Ad-HIV vaccine also stimulates production of anti-HIV antibodies. Together, the regimen induces strong and durable protective responses. We have demonstrated that administration of Ad-HIV vaccine to the upper respiratory tract as well as to the gut (by oral immunization) elicits memory T cells that possess "homing receptors" leading them to traffic to the intestine, a prime site of HIV infection. Thus the vaccine approach elicits cellular immunity at a location critical for preventing or controlling HIV infection. Investigation of combination vaccine approaches using HIV DNA vaccines combined with cytokine adjuvants followed by Ad-HIV vaccine and envelope protein boosting showed them to be immunogenic. The study highlighted several areas that could be optimized for greater protective efficacy against HIV infection. A pre-clinical study in cynomolgus macaques of Mauritian origin identified MHC class I haplotypes associated with natural protection against challenge with a simian immunodeficiency virus (SIV)-HIV chimeric virus (SHIV). These results will enable better design of vaccine studies in this animal model. Further, investigation of such natural host defense mechanisms may suggest new avenues to be exploited for preventive HIV strategies.