State Key Laboratory of Virology, Wuhan Institute of Virology, Chinese Academy of Sciences, Wuhan, 430071, China.
Key Laboratory of Medical Molecular Virology of MOE/MOH, School of Basic Medical Sciences & Shanghai Public Health Clinical Center, Fudan University, Shanghai, 200032, China.
Protein Cell. 2018 Jul;9(7):596-615. doi: 10.1007/s13238-018-0534-7. Epub 2018 Apr 17.
A human immunodeficiency virus type-1 (HIV-1) vaccine which is able to effectively prevent infection would be the most powerful method of extinguishing pandemic of the acquired immunodeficiency syndrome (AIDS). Yet, achieving such vaccine remains great challenges. The membrane-proximal external region (MPER) is a highly conserved region of the envelope glycoprotein (Env) gp41 subunit near the viral envelope surface, and it plays a key role in membrane fusion. It is also the target of some reported broadly neutralizing antibodies (bNAbs). Thus, MPER is deemed to be one of the most attractive vaccine targets. However, no one can induce these bNAbs by immunization with immunogens containing the MPER sequence(s). The few attempts at developing a vaccine have only resulted in the induction of neutralizing antibodies with quite low potency and limited breadth. Thus far, vaccine failure can be attributed to various characteristics of MPER, such as those involving structure and immunology; therefore, we will focus on these and review the recent progress in the field from the following perspectives: (1) MPER structure and its role in membrane fusion, (2) the epitopes and neutralization mechanisms of MPER-specific bNAbs, as well as the limitations in eliciting neutralizing antibodies, and (3) different strategies for MPER vaccine design and current harvests.
一种能够有效预防感染的人类免疫缺陷病毒 1 型（HIV-1）疫苗将是消灭艾滋病（AIDS）大流行的最有效方法。然而，实现这样的疫苗仍然面临巨大的挑战。膜近端外区（MPER）是包膜糖蛋白（Env）gp41 亚基中靠近病毒包膜表面的高度保守区域，它在膜融合中起关键作用。它也是一些报道的广泛中和抗体（bNAbs）的靶标。因此，MPER 被认为是最有吸引力的疫苗靶标之一。然而，没有人可以通过用含有 MPER 序列的免疫原免疫来诱导这些 bNAbs。少数开发疫苗的尝试仅导致诱导中和抗体的效力和广度相当有限。到目前为止，疫苗失败可归因于 MPER 的各种特征，如结构和免疫学特征；因此，我们将重点关注这些特征，并从以下几个方面回顾该领域的最新进展：（1）MPER 结构及其在膜融合中的作用，（2）MPER 特异性 bNAbs 的表位和中和机制，以及诱导中和抗体的局限性，以及（3）MPER 疫苗设计的不同策略和当前的成果。
