【佰通生物专区】PNAS：新型组合性疫苗可免于机体感染HIV

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原文地址链接：PNAS：新型组合性疫苗可免于机体感染HIV   更多精彩新闻请点击：佰通生物

       设计抵御HIV疫苗的目的是保护个体免于HIV感染，然而近年来HIV疫苗的设计往往适得其反，其非但不会帮助个体抵御HIV，反而会增加HIV的感染率，近日，一篇发表在国际杂志PNAS上的研究论文中，来自艾默里大学的研究人员就通过研究表示，疫苗或许会增加HIV病毒靶点作用的免疫细胞的数量，通过对HIV传播的非人类灵长类模型进行研究发现，粘膜组织中较高水平的病毒靶向免疫细胞或许和HIV的高感染率直接相关。
       研究者表示，当我们评估潜在的HIV/AIDS疫苗时，我们或许需要刻意避开可以激活粘膜组织中病毒靶向细胞的路径；难以开发出AIDS疫苗的其中一个原因就是病毒可以感染免疫系统中的免疫细胞，而任何疫苗都是通过诱导免疫系统来发挥作用的。
而研究者们开发HIV疫苗很大一部分都是聚焦于开发可以激活抗病毒T细胞的疫苗，T细胞根据其表面的分子主要分为两类，CD8细胞是杀伤性T细胞的代表，CD4细胞是辅助细胞的代表，CD4+ T细胞是熟知的HIV和SIV作用的靶点，当前有很多研究提出了CD8+ T细胞或许值得深入研究来开发控制HIV感染的策略。
       这项研究中，研究人员利用编码SIV蛋白的5种不同的疫苗组合来免疫猕猴，用于检测细胞介导的机体免疫力的效应，但前提是并不刺激猕猴机体中中和性抗体的产生，在猕猴接受注射16小时和32小时后其又接受了两次加强注射，随后对猕猴重复注射低剂量的SIV，每周一次，注射15次；总的来讲这种免疫体系并不能抑制SIV的感染，但是研究者在所有猕猴机体中都检测到了循环的CD8+ T细胞，而这些细胞和抑制感染无关。
       研究者Silvestri说道，我们发现在感染的猕猴机体的直肠活组织存在大量激活的CD4+ T细胞，本文研究显示，如果这种新型疫苗组合可以诱导活化CD4+ T细胞的产生，那么或许可以在未来帮助开发抵御HIV感染的新型疫苗。

Activated CD4 CCR5 T cells in the rectum predict increased SIV acquisition in SIVGag/Tat-vaccinated rhesus macaques
Diane G. Carnathan, Katherine S. Wetzel, Joana Yu, S. Thera Lee, Brent A. Johnson, Mirko Paiardini, Jian Yan, Matthew P. Morrow, Niranjan Y. Sardesai, David B. Weiner, Hildegund C. J. Ertl, Guido Silvestri
An effective T-cell–based AIDS vaccine should induce strong HIV-specific CD8+ T cells in mucosal tissues without increasing the availability of target cells for the virus. Here, we evaluated five immunization strategies that include Human adenovirus-5 (AdHu5), Chimpanzee adenovirus-6 (AdC6) or -7 (AdC7), Vaccinia virus (VV), and DNA given by electroporation (DNA/EP), all expressing Simian immunodeficiency virus group specific antigen/transactivator of transcription (SIVmac239Gag/Tat). Five groups of six rhesus macaques (RMs) each were vaccinated with DNA/EP-AdC6-AdC7, VV-AdC6-AdC7, DNA/-EP-VV-AdC6, DNA/EP-VV-AdC7, or AdHu5-AdHu5-AdHu5 and were challenged repeatedly with low-dose intrarectal SIVmac239. Upon challenge, there were no significant differences among study groups in terms of virus acquisition or viral load after infection. When taken together, the immunization regimens did not protect against SIV acquisition compared with controls but did result in an ～1.6-log decline in set-point viremia. Although all immunized RMs had detectable SIV-specific CD8+ T cells in blood and rectal mucosa, we found no correlation between the number or function of these SIV-specific CD8+ T cells and protection against SIV acquisition. Interestingly, RMs experiencing breakthrough infection showed significantly higher prechallenge levels of CD4+C-C chemokine receptor type 5 (CCR5)+HLA-DR+ T cells in the rectal biopsies (RB) than animals that remained uninfected. In addition, among the infected RMs, the percentage of CD4+CCR5+Ki-67+ T cells in RBs prechallenge correlated with higher early viremia. Overall, these data suggest that the levels of activated CD4+CCR5+ target T cells in the rectal mucosa may predict the risk of SIV acquisition in RMs vaccinated with vectors that express SIVGag/Tat.