Effects of modification of the HIV-1 Env cytoplasmic tail on immunogenicity of VLP vaccines

被引：17

作者：

Vzorov, Andrei N. ^{[1
]}

Wang, Li

Chen, Jianjun ^{[2
]}

Wang, Bao-Zhong

Compans, Richard W.

机构：

[1] Emory Univ, Sch Med, Dept Microbiol & Immunol, Atlanta, GA 30322 USA

[2] Chinese Acad Sci, Wuhan Inst Virol, State Key Lab Virol, Wuhan 430071, Hunan, Peoples R China

来源：

VIROLOGY | 2016年 / 489卷

基金：

美国国家卫生研究院;

关键词：

HIV-1; VLP vaccine; Env glycoprotein; Cytoplasmic tail; Trimer stability; Neutralizing antibodies; Antibody avidity; Immunogenicity; Protein modification; Cross-Glade immunization; IMMUNODEFICIENCY-VIRUS TYPE-1; ENVELOPE GLYCOPROTEIN COMPLEX; MEMBRANE-SPANNING DOMAIN; CELL FUSION; ANTIBODIES; PROTEINS; GP41; PARTICLES; EPITOPES; STABILIZATION;

D O I：

10.1016/j.virol.2015.09.015

中图分类号：

Q93 [微生物学];

学科分类号：

071005 ; 100705 ;

摘要：

We investigated the effects on assembly and antigenic properties of specific modifications of the transmembrane spanning (TMS) and cytoplasmic tail (CT) domains of HIV-1 Env from a transmitted/ founder (T/F) ZM53 Env glycoprotein. A construct containing a short version of the TMS domain derived from the mouse mammary tumor virus (MMTV) Env with or without a GCN4 trimerization sequence in the CT exhibited the highest levels of incorporation into VLPs and induced the highest titers of anti-Env IgG immune responses in a VLP context. Sera from guinea pigs immunized by VLPs with high Env content, and containing the CT trimerization sequence, had increased neutralization activity and antibody avidity. A cross-Glade prime-boost regimen with Glade B SF162 or Glade C ZM53 Env DNA priming and boosting with VLPs containing modified ZM53 Env further enhanced these immune responses. The modified VLPs demonstrate improved potential as HIV-1 vaccine antigens. (C) 2016 Published by Elsevier Inc.

引用

页码：141 / 150

页数：10

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