一项新的研究报告说，猴子中的某些免疫和遗传学特征可增加某种猴类免疫缺陷病毒（或称SIV）疫苗的有效性。 由于SIV与人类免疫缺陷性病毒（或称HIV）有着密切的关系，这些发现支持这样的观念，即某些人可能带有某些基因或免疫系统的特征，使得他们能够比其他人更好地抵御HIV。

在创制一种有效的HIV疫苗的道路上所遭遇的一个主要障碍是，人们对某个特别的疫苗所产生的有益的免疫反应缺乏了解。 迄今为止， 在HIV疫苗的试验中唯一显示出具有保护性效应的是在2003年至2006年间在泰国开展的RV144试验。

这里，Norman Letvin及其同事立志搞清楚类似的SIV疫苗究竟是如何阻止感染的。 研究人员给一大群的恒河猴接种了SIV疫苗，接着在一个为其2个星期的时间段中，研究人员反复地给这些猴子注射低剂量的SIV。 有一半的猴子产生了对SIV的抵御力，而另外一半的猴子则受到病毒的感染。

接下来，该研究团队在受到保护的猴子中观察了3个层面的免疫反应：细胞免疫反应、先天免疫反应以及抗体反应。 这些猴子的细胞免疫反应和先天免疫反应没有受到疫苗的足够刺激以提供机体保护，但研究人员却在它们的抗体反应有引人注目发现。 低浓度的中和抗体与抵御SIV能力的增加之间具有关联性。 在受到疫苗保护的猴子体内的中和抗体能够与病毒结合并阻断其感染细胞的能力。

研究人员还发现了一种保护性的遗传预测因子：一种叫做TRIM5的基因。 那些机体表达某种形式的TRIM5的猴子能够比没有该基因的猴子更好地抵抗病毒感染。 这两种特质本身都能提供机体保护效应，但兼具基因和免疫特质的猴子能够得到疫苗的最佳保护。

这些结果凸显了在将来参加HIV疫苗试验的志愿者中仔细察看这些免疫和基因特质类型的必要性。

Immune and Genetic Correlates of Vaccine Protection Against Mucosal Infection by SIV in Monkeys

Sci Transl Med 4 May 2011: Vol. 3, Issue 81, p. 81ra36

Abstract

The RV144 vaccine trial in Thailand demonstrated that an HIV vaccine could prevent infection in humans and highlights the importance of understanding protective immunity against HIV. We used a nonhuman primate model to define immune and genetic mechanisms of protection against mucosal infection by the simian immunodeficiency virus (SIV). A plasmid DNA prime/recombinant adenovirus serotype 5 (rAd5) boost vaccine regimen was evaluated for its ability to protect monkeys from infection by SIVmac251 or SIVsmE660 isolates after repeat intrarectal challenges. Although this prime-boost vaccine regimen failed to protect against SIVmac251 infection, 50% of vaccinated monkeys were protected from infection with SIVsmE660. Among SIVsmE660-infected animals, there was about a one-log reduction in peak plasma virus RNA in monkeys expressing the major histocompatibility complex class I allele Mamu-A*01, implicating cytotoxic T lymphocytes in the control of SIV replication once infection is established. Among Mamu-A*01–negative monkeys challenged with SIVsmE660, no CD8⁺ T cell response or innate immune response was associated with protection against virus acquisition. However, low levels of neutralizing antibodies and an envelope-specific CD4⁺ T cell response were associated with vaccine protection in these monkeys. Moreover, monkeys that expressed two TRIM5 alleles that restrict SIV replication were more likely to be protected from infection than monkeys that expressed at least one permissive TRIM5 allele. This study begins to elucidate the mechanisms of vaccine protection against immunodeficiency viruses and highlights the need to analyze these immune and genetic correlates of protection in future trials of HIV vaccine strategies.

来源：EurekAlert中文