title: Microparticles in MF59, a potent adjuvant combination for a recombinant protein vaccine against HIV-1.
abstract: Novel adjuvant formulations involving PLG microparticles with entrapped recombinant protein antigens (env gp120 and p24 gag) from human immunodeficiency virus type-1 (HIV-1), dispersed in the emulsion adjuvant MF59 were evaluated as potential HIV-1 vaccine candidates in mice and baboons. In mice, the adjuvant combination induced significantly enhanced antibody responses in comparison to either adjuvant used alone. In addition, the polylactide co-glycolide polymer (PLG) microparticles and MF59 combination induced CTL activity against HIV-1 p24 gag. In baboons, the adjuvant combination induced significantly enhanced antibody titers after a single dose of gp120, but the responses were comparable to gp120 in MF59 alone after boosting. Both MF59+gp120 alone and PLG/gp120 in MF59 induced neutralizing antibodies against a T cell line-adapted (TCLA) strain and a primary isolate of HIV-1. In contrast to the observations with gp120, immunization in baboons with PLG/p24 in MF59 induced significantly enhanced antibody responses after boosting, in comparison to immunization with MF59 alone + p24.
authors.affiliation: Chiron Corporation, 4560 Horton Street, Emeryville, CA 94608, USA. derek_ohagan@cc.chiron.com
authors.forename: D T
authors.initials: DT
authors.lastname: O'Hagan
authors.forename: M
authors.initials: M
authors.lastname: Ugozzoli
authors.forename: J
authors.initials: J
authors.lastname: Barackman
authors.forename: M
authors.initials: M
authors.lastname: Singh
authors.forename: J
authors.initials: J
authors.lastname: Kazzaz
authors.forename: K
authors.initials: K
authors.lastname: Higgins
authors.forename: T C
authors.initials: TC
authors.lastname: Vancott
authors.forename: G
authors.initials: G
authors.lastname: Ott
mesh_terms: D016915:AIDS Vaccines / Q000008:administration & dosage / Q000276:immunology*; D000276:Adjuvants, Immunologic / Q000008:administration & dosage*; D000818:Animals; D000918:Antibody Specificity; D016466:CHO Cells; D006224:Cricetinae; D004306:Dose-Response Relationship, Immunologic; D004334:Drug Administration Schedule; D005260:Female; D015483:HIV Antibodies / Q000097:blood; D016655:HIV Core Protein p24 / Q000276:immunology; D015699:HIV Envelope Protein gp120 / Q000276:immunology; D015497:HIV-1 / Q000276:immunology*; D007074:Immunoglobulin G / Q000097:blood; D007273:Injections, Intramuscular; D051379:Mice; D008807:Mice, Inbred BALB C; D008863:Microspheres; D010215:Papio; D011136:Polysorbates / Q000008:administration & dosage*; D011994:Recombinant Proteins / Q000276:immunology; D013185:Squalene / Q000008:administration & dosage*; D013602:T-Lymphocytes, Cytotoxic / Q000276:immunology; D014614:Vaccines, Synthetic / Q000008:administration & dosage / Q000276:immunology*
chemical_list: D016915:AIDS Vaccines; D000276:Adjuvants, Immunologic; D015483:HIV Antibodies; D016655:HIV Core Protein p24; D015699:HIV Envelope Protein gp120; D007074:Immunoglobulin G; C089950:MF59 oil emulsion; D011136:Polysorbates; D011994:Recombinant Proteins; D014614:Vaccines, Synthetic; D013185:Squalene