A Prime-Boost Strategy Using Virus-Like Particles Pseudotyped for HCV Proteins Triggers Broadly Neutralizing Antibodies in Macaques

被引：113

作者：

Garrone, Pierre ^{[2
]}

Fluckiger, Anne-Catherine ^{[2
]}

Mangeot, Philippe E. ^{[2
]}

Gauthier, Emmanuel ^{[3
,4
,5
]}

Dupeyrot-Lacas, Pia ^{[2
]}

Mancip, Jimmy ^{[2
]}

Cangialosi, Arnaud ^{[2
]}

Du Chene, Isaure ^{[2
]}

LeGrand, Roger ^{[6
]}

Mangeot, Isabelle ^{[6
]}

Lavillette, Dimitri ^{[3
,4
,5
]}

Bellier, Bertrand ^{[1
,7
,8
]}

Cosset, Francois-Loic ^{[3
,4
,5
]}

Tangy, Frederic ^{[9
]}

Klatzmann, David ^{[1
,7
,8
,10
]}

Dalba, Charlotte ^{[2
,11
]}

机构：

[1] Univ Paris 06, UMR7211, F-75013 Paris, France

[2] Epixis SA, F-69007 Lyon, France

[3] ENS Lyon, F-69007 Lyon, France

[4] Univ Lyon 1, IFR128, F-69007 Lyon, France

[5] INSERM, U785, F-69007 Lyon, France

[6] CEA, Serv Neurovirol DSV DRM, CRSSA, Inst Paris Sud Cytokines, F-92260 Fontenay Aux Roses, France

[7] CNRS, UMR7211, F-75013 Paris, France

[8] Univ Paris 06, INSERM, UMR S959, F-75013 Paris, France

[9] Inst Pasteur, CNRS URA 3015, Dept Virol, Unite Genom Virale & Vaccinat, F-75015 Paris, France

[10] Hop La Pitie Salpetriere, AP HP, F-75013 Paris, France

[11] Epixis SA, F-75013 Paris, France

来源：

SCIENCE TRANSLATIONAL MEDICINE | 2011年 / 3卷 / 94期

基金：

欧洲研究理事会;

关键词：

HEPATITIS-C-VIRUS; CELLULAR-IMMUNE-RESPONSES; ENVELOPE GLYCOPROTEINS; TRANSGENIC MICE; HIV VACCINES; HOST-RANGE; IN-VITRO; INFECTION; DNA; PSEUDOPARTICLES;

D O I：

10.1126/scitranslmed.3002330

中图分类号：

Q2 [细胞生物学];

学科分类号：

071009 ; 090102 ;

摘要：

Chronic hepatitis C virus (HCV) infection, with its cohort of life-threatening complications, affects more than 200 million persons worldwide and has a prevalence of more than 10% in certain countries. Preventive and therapeutic vaccines against HCV are thus much needed. Neutralizing antibodies (NAbs) are the foundation for successful disease prevention for most established vaccines. However, for viruses that cause chronic infection such as HIV or HCV, induction of broad NAbs from recombinant vaccines has remained elusive. We developed a vaccine platform specifically aimed at inducing NAbs based on pseudotyped virus-like particles (VLPs) made with retroviral Gag. We report that VLPs pseudotyped with E2 and/or E1 HCV envelope glycoproteins induced high-titer anti-E2 and/or anti-E1 antibodies, as well as NAbs, in both mouse and macaque. The NAbs, which were raised against HCV 1a, cross-neutralized the five other genotypes tested (1b, 2a, 2b, 4, and 5). Thus, the described VLP platform, which can be pseudotyped with a vast array of virus envelope glycoproteins, represents a new approach to viral vaccine development.

引用

页数：8

共 53 条

[1] A virus-like particle vaccine for epidemic Chikungunya virus protects nonhuman primates against infection [J].