title: Antibody responses after intravaginal immunisation with trimeric HIV-1 CN54 clade C gp140 in Carbopol gel are augmented by systemic priming or boosting with an adjuvanted formulation.
abstract: 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.
authors.affiliation: Centre for Infection and Immunity, Division of Clinical Sciences, St George's, University of London, Cranmer Terrace, London SW17 0RE, UK. mcranage@sgul.ac.uk
authors.forename: Martin P
authors.initials: MP
authors.lastname: Cranage
authors.forename: Carol A
authors.initials: CA
authors.lastname: Fraser
authors.forename: Alethea
authors.initials: A
authors.lastname: Cope
authors.forename: Paul F
authors.initials: PF
authors.lastname: McKay
authors.forename: Michael S
authors.initials: MS
authors.lastname: Seaman
authors.forename: Tom
authors.initials: T
authors.lastname: Cole
authors.forename: A Nasir
authors.initials: AN
authors.lastname: Mahmoud
authors.forename: Joanna
authors.initials: J
authors.lastname: Hall
authors.forename: Elaine
authors.initials: E
authors.lastname: Giles
authors.forename: Gerald
authors.initials: G
authors.lastname: Voss
authors.forename: Mark
authors.initials: M
authors.lastname: Page
authors.forename: Neil
authors.initials: N
authors.lastname: Almond
authors.forename: Robin J
authors.initials: RJ
authors.lastname: Shattock
mesh_terms: D016915:AIDS Vaccines / Q000008:administration & dosage / Q000276:immunology*; D000180:Acrylic Resins; D000276:Adjuvants, Immunologic / Q000008:administration & dosage; D000282:Administration, Intravaginal; D000818:Animals; D057134:Antibodies, Neutralizing / Q000097:blood; D000917:Antibody Formation; D005260:Female; D015483:HIV Antibodies / Q000097:blood; D015658:HIV Infections / Q000276:immunology / Q000517:prevention & control*; D015497:HIV-1 / Q000276:immunology; D018928:Immunity, Mucosal; D007117:Immunization, Secondary; D007273:Injections, Intramuscular; D008252:Macaca fascicularis; D009500:Neutralization Tests; D011145:Polyvinyls / Q000008:administration & dosage; D014621:Vagina / Q000276:immunology / Q000378:metabolism; D054299:env Gene Products, Human Immunodeficiency Virus / Q000276:immunology*
chemical_list: D016915:AIDS Vaccines; D000180:Acrylic Resins; D000276:Adjuvants, Immunologic; D057134:Antibodies, Neutralizing; D015483:HIV Antibodies; D011145:Polyvinyls; D054299:env Gene Products, Human Immunodeficiency Virus; C097729:gp140 envelope protein, Human immunodeficiency virus 1; C006912:carboxypolymethylene