Klasse Per Johan, Sanders Rogier W, Cerutti Andrea, Moore John P
Department of Microbiology and Immunology, Cornell University, Weill Cornell Medical College, New York, New York 10065-4896, USA.
AIDS Res Hum Retroviruses. 2012 Jan;28(1):1-15. doi: 10.1089/aid.2011.0053. Epub 2011 May 20.
No vaccine candidate has induced antibodies (Abs) that efficiently neutralize multiple primary isolates of HIV-1. Preexisting high titers of neutralizing antibodies (NAbs) are essential, because the virus establishes infection before anamnestic responses could take effect. HIV-1 infection elicits Abs against Env, Gag, and other viral proteins, but of these only a subset of the anti-Env Abs can neutralize the virus. Whereas the corresponding proteins from other viruses form the basis of successful vaccines, multiple large doses of HIV-1 Env elicit low, transient titers of Abs that are not protective in humans. The inaccessibility of neutralization epitopes hinders NAb induction, but Env may also subvert the immune response by interacting with receptors on T cells, B cells, monocytes, macrophages, and dendritic cells. Here, we discuss evidence from immunizations of different species with various modified Env constructs. We also suggest how the divergent Ab responses to Gag and Env during infection may reflect differences in B cell regulation. Drawing on these analyses, we outline strategies for improving Env as a component of a vaccine aimed at inducing strong and sustained NAb responses.
尚无候选疫苗能诱导出可有效中和多种HIV-1原始分离株的抗体（Abs）。预先存在高滴度的中和抗体（NAbs）至关重要，因为病毒在记忆反应生效之前就已建立感染。HIV-1感染会引发针对Env、Gag和其他病毒蛋白的抗体，但其中只有一部分抗Env抗体能够中和病毒。虽然其他病毒的相应蛋白构成了成功疫苗的基础，但多次大剂量的HIV-1 Env只能诱导出低水平、短暂的抗体滴度，且这些抗体在人体中并无保护作用。中和表位难以接近阻碍了NAb的诱导，但Env也可能通过与T细胞、B细胞、单核细胞、巨噬细胞和树突状细胞上的受体相互作用来破坏免疫反应。在此，我们讨论了用各种修饰的Env构建体对不同物种进行免疫接种的证据。我们还提出，感染期间对Gag和Env的不同抗体反应可能如何反映B细胞调节的差异。基于这些分析，我们概述了改进Env作为疫苗组分以诱导强烈且持续的NAb反应的策略。
