O'Connor David H, Allen Todd M, Watkins David I
University of Wisconsin at Madison, Department of Pathology, Madison, Wisconsin 53709, USA.
DNA Cell Biol. 2002 Sep;21(9):659-64. doi: 10.1089/104454902760330192.
Several vaccine studies have ameliorated disease progression in simian-human immunodeficiency virus (SHIV) infections. The successes of these vaccines have been largely attributed to protective effects of cytotoxic T-lymphocyte (CTL) responses, although the precise correlates of immune protection remain poorly defined. It is now well established that vigorous CTL and antibody responses can rapidly select for viral escape variants after HIV and SIV infection. Here we suggest that viral variation analyses should be performed on viruses derived from vaccinated, SIV-, or SHIV-challenged animals as a routine component of vaccine evaluation to determine the contribution of immune responses to the success (or failure) of the vaccine regimen. To illustrate the importance of escape analysis, we show that rapid emergence of escape variants postchallenge contributed to the failure of a DNA prime/MVA boost vaccine regimen encoding SIV Tat.
多项疫苗研究改善了猿猴-人类免疫缺陷病毒(SHIV)感染中的疾病进展。这些疫苗的成功很大程度上归因于细胞毒性T淋巴细胞(CTL)反应的保护作用,尽管免疫保护的确切相关因素仍不清楚。现已明确,HIV和SIV感染后,强烈的CTL和抗体反应可迅速选择出病毒逃逸变异株。在此我们建议,作为疫苗评估的常规组成部分,应对来自接种疫苗、感染SIV或SHIV的动物的病毒进行病毒变异分析,以确定免疫反应对疫苗方案成功(或失败)的贡献。为说明逃逸分析的重要性,我们表明,攻击后逃逸变异株的快速出现导致了一种编码SIV Tat的DNA初免/MVA加强疫苗方案的失败。