title: Repeated vaginal administration of trimeric HIV-1 clade C gp140 induces serum and mucosal antibody responses.
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.
authors.affiliation: Centre for Infection, Division of Cellular and Molecular Medicine, St George's University of London, London, UK. mcranage@sgul.ac.uk
authors.forename: M P
authors.initials: MP
authors.lastname: Cranage
authors.forename: C A
authors.initials: CA
authors.lastname: Fraser
authors.forename: Z
authors.initials: Z
authors.lastname: Stevens
authors.forename: J
authors.initials: J
authors.lastname: Huting
authors.forename: M
authors.initials: M
authors.lastname: Chang
authors.forename: S A
authors.initials: SA
authors.lastname: Jeffs
authors.forename: M S
authors.initials: MS
authors.lastname: Seaman
authors.forename: A
authors.initials: A
authors.lastname: Cope
authors.forename: T
authors.initials: T
authors.lastname: Cole
authors.forename: R J
authors.initials: RJ
authors.lastname: Shattock
mesh_terms: D000282:Administration, Intravaginal; D000818:Animals; D000917:Antibody Formation; D002460:Cell Line; D018604:Epitope Mapping; D000939:Epitopes / Q000378:metabolism; D015483:HIV Antibodies / Q000097:blood; D015658:HIV Infections / Q000097:blood / Q000276:immunology* / Q000517:prevention & control; D015497:HIV-1 / Q000276:immunology* / Q000472:pathogenicity; D006801:Humans; D018928:Immunity, Mucosal; D007114:Immunization; D011817:Rabbits; D054299:env Gene Products, Human Immunodeficiency Virus / Q000008:administration & dosage / Q000276:immunology*
chemical_list: D000939:Epitopes; D015483:HIV Antibodies; D054299:env Gene Products, Human Immunodeficiency Virus; C097729:gp140 envelope protein, Human immunodeficiency virus 1