Antibody responses after intravaginal immunisation with trimeric HIV-1CN54 clade C gp140 in Carbopol gel are augmented by systemic priming or boosting with an adjuvanted formulation

被引：33

作者：

Cranage, Martin P. ^{[1
]}

Fraser, Carol A. ^{[1
]}

Cope, Alethea ^{[1
]}

McKay, Paul F. ^{[1
]}

Seaman, Michael S. ^{[2
]}

Cole, Tom ^{[1
]}

Mahmoud, A. Nasir ^{[1
]}

Hall, Joanna ^{[3
]}

Giles, Elaine ^{[3
]}

Voss, Gerald ^{[4
]}

Page, Mark ^{[3
]}

Almond, Neil ^{[3
]}

Shattock, Robin J. ^{[1
]}

机构：

[1] Univ London, Div Clin Sci, Ctr Infect & Immun, London SW17 0RE, England

[2] Harvard Univ, Beth Israel Deaconess Med Ctr, CAVD Neutralizing Antibody Lab, Sch Med, Boston, MA 02215 USA

[3] Natl Inst Biol Stand & Controls, Div Retrovirol, Potters Bar EN6 3QG, Herts, England

[4] GlaxoSmithKline Biol, Rixensart, Belgium

来源：

VACCINE | 2011年 / 29卷 / 07期

基金：

比尔及梅琳达.盖茨基金会; 英国惠康基金;

关键词：

Immunisation; Vagina; HIV-gp140; IMMUNODEFICIENCY-VIRUS; HIV-1; VACCINE; SECRETING CELLS; VAGINAL TRANSMISSION; CERVICAL SECRETIONS; RECOMBINANT GP120; IMMUNE-RESPONSE; MUCOSAL; TYPE-1; MACAQUES;

D O I：

10.1016/j.vaccine.2010.12.034

中图分类号：

R392 [医学免疫学]; Q939.91 [免疫学];

学科分类号：

100102 ;

摘要：

Optimum strategies to elicit and maintain antibodies at mucosal portals of virus entry are critical for the development of vaccines against human immunodeficiency virus (HIV). Here we show in non-human primates that a novel regimen of repeated intravaginal delivery of a non-adjuvanted, soluble recombinant trimeric HIV-1(CN54) clade C envelope glycoprotein (gp140) administered in Carbopol gel can prime for B-cell responses even in the absence of seroconversion. Following 3 cycles of repeated intravaginal administration, throughout each intermenses interval, 3 of 4 macaques produced or boosted systemic and mucosally-detected antibodies upon intramuscular immunisation with gp140 formulated in AS01 adjuvant. Reciprocally, a single intramuscular immunisation primed 3 of 4 macaques for antibody boosting after a single cycle of intravaginal immunisation. Virus neutralising activity was detected against clade C and clade B HIV-1 envelopes but was restricted to highly neutralisation sensitive pseudoviruses. (C) 2010 Elsevier Ltd. All rights reserved.

引用

页码：1421 / 1430

页数：10

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