An adenovirus-based HIV subtype B prime/boost vaccine regimen elicits antibodies mediating broad antibody-dependent cellular cytotoxicity against non-subtype B HIV strains.

Published

Journal Article

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.

Full Text

Duke Authors

Cited Authors

  • Gómez-Román, VR; Florese, RH; Peng, B; Montefiori, DC; Kalyanaraman, VS; Venzon, D; Srivastava, I; Barnett, SW; Robert-Guroff, M

Published Date

  • November 1, 2006

Published In

Volume / Issue

  • 43 / 3

Start / End Page

  • 270 - 277

PubMed ID

  • 16940858

Pubmed Central ID

  • 16940858

International Standard Serial Number (ISSN)

  • 1525-4135

Digital Object Identifier (DOI)

  • 10.1097/01.qai.0000230318.40170.60

Language

  • eng

Conference Location

  • United States