Davenport Miles P, Loh Liyen, Petravic Janka, Kent Stephen J
Centre for Vascular Research, University of NSW, Kensington, NSW 2052, Australia.
Trends Microbiol. 2008 Dec;16(12):561-6. doi: 10.1016/j.tim.2008.09.001. Epub 2008 Oct 27.
HIV-1 mutates extensively in vivo to escape immune control by CD8+ T cells (CTLs). The CTL escape mutant virus might also revert back to wild-type upon transmission to new hosts if significant fitness costs are incurred by the mutation. Immune escape and reversion can be extremely fast if they occur very early after infection, whereas they are much slower when they begin later during infection. Immune escape presents a significant barrier to vaccination, because escape of vaccine-mediated immune responses could neutralise any benefits of vaccination. Here, we consider the dynamics of immune escape and reversion in vivo in natural infection, and suggest how understanding of this can be used to predict optimal vaccine targets and design vaccination strategies that maximise immune control. We predict that inducing synchronous, broad CTL by vaccination should limit the likelihood of viral escape from immune control.
HIV-1在体内会广泛突变以逃避CD8 + T细胞（CTL）的免疫控制。如果突变导致显著的适应性代价，CTL逃逸突变病毒在传播到新宿主时也可能恢复为野生型。如果免疫逃逸和恢复在感染后很早发生，它们可能会极其迅速，而在感染后期开始时则要慢得多。免疫逃逸对疫苗接种构成了重大障碍，因为疫苗介导的免疫反应的逃逸可能会抵消疫苗接种的任何益处。在这里，我们考虑自然感染中体内免疫逃逸和恢复的动态，并提出如何利用对此的理解来预测最佳疫苗靶点并设计能最大限度增强免疫控制的疫苗接种策略。我们预测，通过疫苗接种诱导同步、广泛的CTL应能限制病毒从免疫控制中逃逸的可能性。
