Keckler M Shannon, Hodara Vida L, Parodi Laura M, Giavedoni Luis D
University of Texas Health Science Center at San Antonio, Texas., Department of Virology and Immunology, San Antonio, Texas, USA.
Viral Immunol. 2007 Dec;20(4):623-34. doi: 10.1089/vim.2007.0068.
Infection of rhesus macaques with simian immunodeficiency virus (SIV) is the preferred animal model for the development and testing of human immunodeficiency virus (HIV) vaccines, and animals protected from SIV challenge by live attenuated vaccines are an invaluable tool for determining immune correlates of protection. The acute phase of SIV infection, in which immune responses are most critical for slowing disease progression, occurs within the first 4 weeks of exposure. The small window of time available for observing critical immune responses makes obtaining adequate blood samples with sufficient frequency difficult. This study is the first to apply a previously reported nonhuman primate (NHP) tether system to study viral immunology. The use of the tether allows for frequent blood sampling without using restraints or sedation, thereby reducing the potentially confounding physiological changes induced by stress. We performed comparative analysis of acute phase immune responses in vaccinated and unvaccinated animals challenged with SIV-mac251. Our results demonstrate live attenuated vaccine-induced protection, which is associated with small increases in the cytotoxic T-cell (CTL) response to immunodominant epitopes, but not with increases in antibody titers. Additionally, vaccination was shown to establish a pool of antigen-specific CD8+ memory cells available for expansion after challenge. The confirmatory nature of these data indicates the validity of using the tether system for evaluation of acute phase anti-SIV responses and can be applied to the study of immune responses in other viral infections in which frequent sampling in small windows of time would be useful.
恒河猴感染猴免疫缺陷病毒（SIV）是开发和测试人类免疫缺陷病毒（HIV）疫苗的首选动物模型，通过减毒活疫苗免受SIV攻击的动物是确定保护的免疫相关因素的宝贵工具。SIV感染的急性期发生在接触后的前4周内，在此期间免疫反应对于减缓疾病进展最为关键。可用于观察关键免疫反应的时间窗口很小，因此难以以足够的频率获取足够的血样。本研究首次应用先前报道的非人灵长类动物（NHP）系留系统来研究病毒免疫学。使用系留装置可在不使用约束或镇静的情况下频繁采集血样，从而减少应激引起的潜在混杂生理变化。我们对用SIV-mac251攻击的接种疫苗和未接种疫苗的动物的急性期免疫反应进行了比较分析。我们的结果表明减毒活疫苗诱导了保护作用，这与针对免疫显性表位的细胞毒性T细胞（CTL）反应略有增加有关，但与抗体滴度的增加无关。此外，接种疫苗显示可建立一组抗原特异性CD8 +记忆细胞，在受到攻击后可用于扩增。这些数据的证实性质表明使用系留系统评估急性期抗SIV反应的有效性，并且可应用于研究其他病毒感染中的免疫反应，在这些感染中，在小时间窗口内频繁采样将是有用的。
