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An Adenovirus-Based HIV Subtype B Prime/Boost Vaccine Regimen Elicits Antibodies Mediating Broad Antibody-Dependent Cellular Cytotoxicity Against Non-Subtype B HIV Strains

Gómez-Román, V. Raúl PhD*†; Florese, Ruth H PhD*; Peng, Bo PhD*; Montefiori, David C PhD; Kalyanaraman, Vaniambadi S PhD§; Venzon, David PhD; Srivastava, Indresh PhD; Barnett, Susan W PhD; Robert-Guroff, Marjorie PhD*

JAIDS Journal of Acquired Immune Deficiency Syndromes: November 1st, 2006 - Volume 43 - Issue 3 - p 270-277
doi: 10.1097/01.qai.0000230318.40170.60
Basic Science

Summary: 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 gp140ΔV2 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.

Received for publication March 25, 2006; accepted May 22, 2006.

From the *Vaccine Branch, Center for Cancer Research, National Cancer Institute, National Institutes of Health, Bethesda, MD; †Novartis Vaccines, Emeryville, CA; ‡Department of Surgery, Duke University Medical Center, Durham, NC; §Advanced BioScience Laboratories, Inc., Kensington, MD; and ‖Biostatistics and Data Management Section, Center for Cancer Research, National Cancer Institute, National Institutes of Health, Bethesda, MD.

Supported by National Institute of Allergy and Infectious Diseases, National Institute of Health (NIH) grant P01 AI48225-03 to Chiron Corporation and, in part, by the Intramural Research Program of the NIH, National Cancer Institute, Center for Cancer Research.

Reprints: Marjorie Robert-Guroff, PhD, National Institutes of Health, National Cancer Institute, 41 Medlars Drive, Building 41, Room D804, Bethesda, MD 20892-5065 (e-mail: guroffm@mail.nih.gov).

© 2006 Lippincott Williams & Wilkins, Inc.