Requirements for the Induction of Broadly Neutralizing Antibodies against HIV-1 by Vaccination

被引：2

作者：

Vzorov, A. N. ^{[1
]}

Uryvaev, L. V. ^{[1
]}

机构：

[1] Gamaleya Fed Res Ctr Epidemiol & Microbiol, Ivanovsky Inst Virol, Moscow 123098, Russia

来源：

MOLECULAR BIOLOGY | 2017年 / 51卷 / 06期

关键词：

HIV-1; broadly neutralizing antibodies; protective neutralizing antibodies; Env trimer; virus-like particles; IMMUNODEFICIENCY-VIRUS TYPE-1; B-CELL RECEPTORS; ENVELOPE GLYCOPROTEIN TRIMERS; HUMAN MONOCLONAL-ANTIBODIES; HELPER T-CELLS; CYTOPLASMIC TAIL; NONNEUTRALIZING ANTIBODIES; POTENT NEUTRALIZATION; GERMINAL-CENTERS; IMMUNE-RESPONSES;

D O I：

10.1134/S0026893317060176

中图分类号：

Q5 [生物化学]; Q7 [分子生物学];

学科分类号：

071010 ; 081704 ;

摘要：

A study of the induction of broadly neutralizing antibodies (bNAbs) in HIV-infected patients and vaccinated subjects revealed the main criteria for the formation of bNAbs (the duration of exposure to a viral antigen, the effect of the diversity of HIV variants, and the removal of barriers associated with the Env-dependent defense mechanisms of HIV-1). Modified trimers of the HIV-1 envelope protein (Env) exposed on virus-like particles (VLP) have unique properties: they (i) modulate the exposure of binding sites (bs) of the CD4 receptor and co-receptor; (ii) create steric restrictions for contact with bNAbs; (iii) increase the Env presentation density, thus enhancing the immune response; (iv) form stable trimers that do not induce off-target immune responses; and (v) allow additional modifications to their structure and construction of a platform with immunostimulating molecules. Immunization using a heterologous subtype-cross prime-boost regime with modified trimeric Env is capable of inducing somatic hypermutation levels necessary for the formation of bNAbs.

引用

页码：819 / 829

页数：11

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