Repeated vaginal administration of trimeric HIV-1 clade C gp140 induces serum and mucosal antibody responses

被引:33
作者
Cranage, M. P. [1 ]
Fraser, C. A. [1 ]
Stevens, Z. [1 ]
Huting, J. [1 ]
Chang, M. [1 ,2 ]
Jeffs, S. A. [3 ]
Seaman, M. S. [4 ]
Cope, A. [1 ]
Cole, T. [1 ]
Shattock, R. J. [1 ]
机构
[1] St Georges Univ London, Ctr Infect, Div Cellular & Mol Med, London, England
[2] Polymun Sci Immunbiol Forsch GmbH, Vienna, Austria
[3] Univ London Imperial Coll Sci Technol & Med, Jefferiss Res Trust Labs, Wright Fleming Inst, Div Med, London, England
[4] Harvard Univ, Beth Israel Deaconess Med Ctr, Sch Med, CAVD Neutralizing Antibody Lab, Boston, MA 02215 USA
基金
比尔及梅琳达.盖茨基金会;
关键词
HUMAN-IMMUNODEFICIENCY-VIRUS; FEMALE GENITAL-TRACT; NEUTRALIZING ANTIBODIES; ENVELOPE PROTEINS; TYPE-1; IMMUNIZATION; INFECTION; VACCINE; TRANSMISSION; INDUCTION;
D O I
10.1038/mi.2009.110
中图分类号
R392 [医学免疫学]; Q939.91 [免疫学];
学科分类号
100102 ;
摘要
Vaccine-mediated prevention of primary infection with human immunodeficiency virus (HIV) may require the sustained production of antibody at mucosal portals of entry. Here, we describe a novel approach of repeated mucosal immunization by delivering an HIV-1 envelope glycoprotein (gp) in a gel formulated for intravaginal delivery. Rabbits were immunized over one to three 19-day cycles of intravaginal dosing with soluble recombinant trimeric HIV-1 clade C gp140 administered in Carbopol gel. The formulation was well tolerated. A single immunization cycle induced immunoglobulin G (IgG) antibody detected in the serum and female genital tract, and titers were boosted on further immunization. Vaccine-induced serum antibodies neutralized the infectivity of a pseudovirus carrying a heterologous clade C envelope. Our data prove the concept that repeated exposure of the female genital tract to HIV envelope can induce mucosally detectable antibody.
引用
收藏
页码:57 / 68
页数:12
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