The development of HIV vaccines targeting gp41 membrane-proximal external region (MPER): challenges and prospects.
10.1007/s13238-018-0534-7
- Author:
Huan LIU
1
;
Xiaojie SU
2
;
Lulu SI
2
;
Lu LU
3
;
Shibo JIANG
4
Author Information
1. State Key Laboratory of Virology, Wuhan Institute of Virology, Chinese Academy of Sciences, Wuhan, 430071, China. liuhuan@wh.iov.cn.
2. Key Laboratory of Medical Molecular Virology of MOE/MOH, School of Basic Medical Sciences & Shanghai Public Health Clinical Center, Fudan University, Shanghai, 200032, China.
3. Key Laboratory of Medical Molecular Virology of MOE/MOH, School of Basic Medical Sciences & Shanghai Public Health Clinical Center, Fudan University, Shanghai, 200032, China. lul@fudan.edu.cn.
4. Key Laboratory of Medical Molecular Virology of MOE/MOH, School of Basic Medical Sciences & Shanghai Public Health Clinical Center, Fudan University, Shanghai, 200032, China. shibojiang@fudan.edu.cn.
- Publication Type:Journal Article
- Keywords:
ADCC;
HIV-1;
MPER;
gp41;
neutralizing antibodies;
vaccine
- MeSH:
AIDS Vaccines;
chemistry;
immunology;
Antibodies, Neutralizing;
immunology;
HIV Antibodies;
immunology;
HIV Envelope Protein gp41;
immunology;
HIV-1;
chemistry;
immunology;
Humans
- From:
Protein & Cell
2018;9(7):596-615
- CountryChina
- Language:English
-
Abstract:
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.
