Volume 9 Issue 7
Jul.  2018
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Huan Liu, Xiaojie Su, Lulu Si, Lu Lu, Shibo Jiang. The development of HIV vaccines targeting gp41 membrane-proximal external region (MPER): challenges and prospects[J]. Protein&Cell, 2018, 9(7): 596-615. doi: 10.1007/s13238-018-0534-7
Citation: Huan Liu, Xiaojie Su, Lulu Si, Lu Lu, Shibo Jiang. The development of HIV vaccines targeting gp41 membrane-proximal external region (MPER): challenges and prospects[J]. Protein&Cell, 2018, 9(7): 596-615. doi: 10.1007/s13238-018-0534-7

The development of HIV vaccines targeting gp41 membrane-proximal external region (MPER): challenges and prospects

doi: 10.1007/s13238-018-0534-7
Funds:  This work was supported by the National Natural Science Foundation of China (Grant Nos. 81661128041 and 81672019 to L. Lu; 81630090 to S. Jiang), Shanghai Rising-Star Program (16QA1400300) and Wuhan Science and Technology Project (2016060101010066). We also thank Guangzhou SageneBiotech Co., LTD for helping us draw pictures.
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  • 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.
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