Lü X, Kiyono H, Lu D, Kawabata S, Torten J, Srinivasan S, Dailey P J, McGhee J R, Lehner T, Miller C J
California Regional Primate Research Center, School of Veterinary Medicine, University of California Davis, USA.
AIDS. 1998 Jan 1;12(1):1-10. doi: 10.1097/00002030-199801000-00001.
Sexual transmission of HIV is the most common route of HIV transmission throughout the world. To prevent sexually transmitted HIV infection, a vaccine is urgently needed. A previous report demonstrated the targeted immunization of the iliac lymph nodes with simian immunodeficiency virus (SIV) subunits protects rhesus macaques from rectal challenge with SIV. We sought to determine whether this immunization strategy could protect rhesus macaques from vaginal challenge with SIV.
Macaques were immunized with either whole-killed SIV or envelope and core subunit antigen vaccines. Using three independent groups, with three macaques in each group, macaques were immunized by the targeted iliac lymph-node (TILN) route, injecting the vaccine close to the iliac lymph nodes that drain the genital tract.
The TILN immunization procedure induced high-titer SIV-specific immunoglobulin (Ig) G antibodies in serum in all animals and anti-SIV IgG and IgA antibodies in the cervicovaginal secretions of most animals. After a series of three or four TILN immunizations, the animals were intravaginally challenged with SIVmac251. All animals became virus isolation-positive, except one animal immunized with SIV p27 and gp120. This animal was virus isolation-negative but SIV DNA proviral sequences were detected in peripheral blood mononuclear cells.
In this series of studies, reliable protection from vaginal transmission of SIV was not achieved by the TILN immunization procedure.
在全球范围内,艾滋病毒的性传播是最常见的传播途径。为预防通过性传播的艾滋病毒感染,迫切需要一种疫苗。先前的一份报告表明,用猴免疫缺陷病毒(SIV)亚基对髂淋巴结进行靶向免疫可保护恒河猴免受SIV直肠攻击。我们试图确定这种免疫策略是否能保护恒河猴免受SIV阴道攻击。
用全灭活SIV或包膜及核心亚基抗原疫苗对猕猴进行免疫。使用三个独立的组,每组三只猕猴,通过靶向髂淋巴结(TILN)途径进行免疫,即将疫苗注射到引流生殖道的髂淋巴结附近。
TILN免疫程序在所有动物血清中诱导出高滴度的SIV特异性免疫球蛋白(Ig)G抗体,在大多数动物的宫颈阴道分泌物中诱导出抗SIV IgG和IgA抗体。经过一系列三到四次TILN免疫后,动物经阴道接受SIVmac251攻击。除一只用SIV p27和gp120免疫的动物外,所有动物病毒分离均呈阳性。这只动物病毒分离呈阴性,但在外周血单个核细胞中检测到SIV DNA前病毒序列。
在这一系列研究中,TILN免疫程序未能实现对SIV阴道传播的可靠保护。