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

反复阴道给药三聚体 HIV-1 进化枝 C gp140 可诱发血清和粘膜抗体反应

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作者:M P Cranage, C A Fraser, Z Stevens, J Huting, M Chang, S A Jeffs, M S Seaman, A Cope, T Cole, R J Shattock

Abstract

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.

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