title: Neutralizing antibody responses to subtype B and C adjuvanted HIV envelope protein vaccination in rabbits.
abstract: Improving the potency, breadth, and durability of neutralizing antibody responses to HIV are major challenges for HIV vaccine development. To address these challenges, the studies described evaluate in rabbits the titers, breadth, and epitope specificities of antibody responses elicited by HIV envelope subunit vaccines adjuvanted with MF59 with or without CpG oligodeoxynucleotide (ODN). Animals were immunized with trimeric o-gp140DeltaV2 derived from subtype B HIV-1(SF162) or subtype C HIV-1(TV1), or proteins from both strains. Immunization with SF162 or TV1 with MF59/CpG elicited higher titers of binding and neutralizing antibodies to SF162 than monovalent immunization with MF59 alone (P<0.01). Bivalent immunization increased binding and neutralizing antibody titers over single envelope immunization in MF59 (P<0.01). Bivalent immunization also improved neutralization breadth. Epitope mapping indicated neutralizing activity in rabbits was directed to V3 and V4. Overall, our data suggests that a multivalent vaccination approach with MF59 and CpG can enhance humoral responses to HIV-1.
authors.affiliation: Novartis Vaccines and Diagnostics, 4560 Horton Street, Emeryville, California 94608, USA.
authors.forename: Brian
authors.initials: B
authors.lastname: Burke
authors.forename: Victor Raúl
authors.initials: VR
authors.lastname: Gómez-Román
authors.forename: Ying
authors.initials: Y
authors.lastname: Lian
authors.forename: Yide
authors.initials: Y
authors.lastname: Sun
authors.forename: Elaine
authors.initials: E
authors.lastname: Kan
authors.forename: Jeffrey
authors.initials: J
authors.lastname: Ulmer
authors.forename: Indresh K
authors.initials: IK
authors.lastname: Srivastava
authors.forename: Susan W
authors.initials: SW
authors.lastname: Barnett
mesh_terms: D016915:AIDS Vaccines / Q000276:immunology*; D000276:Adjuvants, Immunologic; D000818:Animals; D000914:Antibodies, Viral / Q000276:immunology*; D000917:Antibody Formation / Q000276:immunology; D004353:Drug Evaluation, Preclinical; D015658:HIV Infections / Q000276:immunology* / Q000517:prevention & control; D015497:HIV-1 / Q000276:immunology*; D009500:Neutralization Tests; D009838:Oligodeoxyribonucleotides / Q000276:immunology; D011136:Polysorbates; D011817:Rabbits; D013185:Squalene / Q000276:immunology; D014611:Vaccination; D054299:env Gene Products, Human Immunodeficiency Virus / Q000235:genetics / Q000276:immunology*
chemical_list: D016915:AIDS Vaccines; D000276:Adjuvants, Immunologic; D000914:Antibodies, Viral; C089950:MF59 oil emulsion; D009838:Oligodeoxyribonucleotides; D011136:Polysorbates; D054299:env Gene Products, Human Immunodeficiency Virus; D013185:Squalene