title: An adenovirus-based HIV subtype B prime/boost vaccine regimen elicits antibodies mediating broad antibody-dependent cellular cytotoxicity against non-subtype B HIV strains.
abstract: Although HIV subtype B predominates in North America and Western Europe, most HIV infections worldwide are non-subtype B. Globally effective AIDS vaccines need to elicit broad immunity against multiple HIV strains. In this study, 10 chimpanzees were intranasally primed sequentially with adenovirus type 5 (Ad5)- and Ad7-HIVMNenv/rev recombinants and boosted twice intramuscularly with heterologous oligomeric HIVSF162 gp140DeltaV2 protein in MF59 adjuvant. Sera were evaluated for binding, neutralizing, and antibody-dependent cellular cytotoxicity (ADCC) against HIV clades A, B, C, and CRF01_AE. The vaccine regimen elicited high-titered HIV subtype A, B, C and CRF01_AE gp120-binding antibodies. Sera from 7 of 10 vaccinated chimpanzees cross-neutralized the heterologous South African subtype C primary HIVTV-1 isolate. Significant cross-clade neutralization against other subtype A, C and E isolates was not observed. Sera from all animals mediated ADCC of cells coated with gp120 from HIV subtypes A and B. Nine of 10 animals also exhibited ADCC activity against HIV subtype C and CRF01_AE gp120-coated targets. This subtype B Ad-HIV recombinant prime/envelope protein boost regimen is a promising approach for eliciting broad ADCC activity against diverse HIV clades. Incorporating additional non-subtype B envelope genes and protein boosts in a multivalent strategy may be required to elicit broader neutralizing antibodies against non-subtype B HIV strains.
authors.affiliation: Vaccine Branch, Center for Cancer Research, National Cancer Institute, National Institutes of Health, Bethesda, MD 20892-5065, USA.
authors.forename: V Raúl
authors.initials: VR
authors.lastname: Gómez-Román
authors.forename: Ruth H
authors.initials: RH
authors.lastname: Florese
authors.forename: Bo
authors.initials: B
authors.lastname: Peng
authors.forename: David C
authors.initials: DC
authors.lastname: Montefiori
authors.forename: Vaniambadi S
authors.initials: VS
authors.lastname: Kalyanaraman
authors.forename: David
authors.initials: D
authors.lastname: Venzon
authors.forename: Indresh
authors.initials: I
authors.lastname: Srivastava
authors.forename: Susan W
authors.initials: SW
authors.lastname: Barnett
authors.forename: Marjorie
authors.initials: M
authors.lastname: Robert-Guroff
mesh_terms: D016915:AIDS Vaccines / Q000008:administration & dosage / Q000276:immunology*; D000256:Adenoviridae / Q000235:genetics; D000818:Animals; D003429:Cross Reactions; D004353:Drug Evaluation, Preclinical; D005822:Genetic Vectors / Q000276:immunology; D015483:HIV Antibodies / Q000097:blood / Q000276:immunology*; D015699:HIV Envelope Protein gp120 / Q000276:immunology; D015658:HIV Infections / Q000276:immunology / Q000517:prevention & control; D015497:HIV-1 / Q000145:classification / Q000235:genetics / Q000276:immunology*; D007117:Immunization, Secondary; D009500:Neutralization Tests; D002679:Pan troglodytes; D011994:Recombinant Proteins / Q000276:immunology; D014614:Vaccines, Synthetic / Q000276:immunology; D014765:Viral Vaccines / Q000008:administration & dosage
chemical_list: D016915:AIDS Vaccines; D015483:HIV Antibodies; D015699:HIV Envelope Protein gp120; D011994:Recombinant Proteins; D014614:Vaccines, Synthetic; D014765:Viral Vaccines