Pinter Abraham
Public Health Research Institute, New Jersey Medical School, University of Medicine and Dentistry of New Jersey, Newark, NJ 07103-3535, USA.
Curr HIV Res. 2007 Nov;5(6):542-53. doi: 10.2174/157016207782418470.
A major focus of HIV-1 vaccine development has been directed towards a limited number of broadly conserved epitopes in the Envelope (Env) proteins that are sensitive neutralization targets in many primary isolates. However, evidence suggests that these epitopes are poorly immunogenic; similar antibodies are rarely produced by infected subjects, nor are they induced by various immunogens designed to express these epitopes. On the other hand, the major variable domains of Env are highly immunogenic; antibodies against these regions are common in sera of infected patients and easily generated upon immunization. Although these epitopes are extremely sensitive neutralization targets in some laboratory strains and primary isolates, the neutralization range of antibodies against these sites is limited. This review describes potent neutralization epitopes located in the variable regions of Env and discusses the bases for the limited neutralization breadth of antibodies against these targets. Strategies are discussed for using available information to design immunogens capable of exploiting the potential of these regions as vaccine targets.
HIV-1疫苗研发的一个主要重点一直是针对包膜（Env）蛋白中数量有限的广泛保守表位，这些表位在许多原代分离株中是敏感的中和靶点。然而，有证据表明这些表位免疫原性较差；受感染个体很少产生类似的抗体，旨在表达这些表位的各种免疫原也无法诱导产生此类抗体。另一方面，Env的主要可变结构域具有高度免疫原性；针对这些区域的抗体在感染患者的血清中很常见，免疫后也很容易产生。尽管这些表位在一些实验室毒株和原代分离株中是极其敏感的中和靶点，但针对这些位点的抗体中和范围有限。本综述描述了位于Env可变区的有效中和表位，并讨论了针对这些靶点的抗体中和广度有限的原因。还讨论了利用现有信息设计免疫原的策略，这些免疫原能够发挥这些区域作为疫苗靶点的潜力。
