Aldovini Anna
Boston Children's Hospital, 300 Longwood Ave., Boston, MA 02115, USA.
Curr HIV Res. 2016;14(3):247-59. doi: 10.2174/1570162x14999160224103025.
Most of HIV infections occur via the genital tract or the rectum and HIV replicates at high levels in lymphoid organs and intestinal mucosa, likely requiring a more diversified immunity than pathogens restricted to a single mucosal site, such as the gastrointestinal tract for Vibrio cholera, or the respiratory airways for the influenza virus.
Numerous AIDS vaccine candidates are under development and a general observation obtained from preclinical trials in non-human primates that failed to provide sterilizing immunity is that some infection protection or delayed onset of disease is observed in the presence of anti-SIV immunity. Recent clinical trials support difficulties to reproduce in humans the results observed in simian models, but at least one of them indicated that some protection of infection can be achieved. However, given the limited efficacy observed in the RV144 trial and concerns voiced in its statistical interpretation, preclinical trials should explore more effective immunogens, whether new or as combinations of existing ones, and mucosal routes of vaccinations in addition to the systemic routes, with the goal to maximize vaccination-mediated protection.
The rationale for generating both strong mucosal and systemic immunity comes from animal experiments, recent clinical trials, and other successful vaccines currently in use. Mucosal responses against SIV have been induced with a variety of SIV antigens and via different mucosal routes with a spectrum of effects on protection. This review covers the rational and the experimental data that support the validity to explore mucosal immunization for HIV infection and AIDS prevention.
大多数HIV感染通过生殖道或直肠发生,HIV在淋巴器官和肠道黏膜中大量复制,可能需要比局限于单一黏膜部位的病原体(如霍乱弧菌的胃肠道或流感病毒的呼吸道)更为多样化的免疫反应。
众多艾滋病疫苗候选物正在研发中,从未能提供无菌免疫的非人类灵长类动物的临床前试验中获得的一个普遍观察结果是,在存在抗SIV免疫的情况下,可观察到一定的感染保护或疾病发病延迟。近期的临床试验证实,在人类中重现猿猴模型中观察到的结果存在困难,但至少其中一项试验表明可以实现一定程度的感染保护。然而,鉴于RV144试验中观察到的疗效有限以及对其统计解读存在的担忧,临床前试验应探索更有效的免疫原,无论是新的免疫原还是现有免疫原的组合,除了全身途径外,还应探索黏膜接种途径,目标是使疫苗介导的保护最大化。
产生强大的黏膜免疫和全身免疫的理论依据来自动物实验、近期的临床试验以及目前正在使用的其他成功疫苗。已通过多种SIV抗原并经由不同黏膜途径诱导了针对SIV的黏膜反应,对保护产生了一系列影响。本综述涵盖了支持探索针对HIV感染和艾滋病预防的黏膜免疫有效性的理论依据和实验数据。