Journal
JOURNAL OF IMMUNOLOGY
Volume 182, Issue 10, Pages 6587-6599Publisher
AMER ASSOC IMMUNOLOGISTS
DOI: 10.4049/jimmunol.0900317
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Funding
- National Institutes of Health [P01AI052271, U19AI074078, U19 AI074078]
- Wistar Institute
- U.S. National Cancer Institute Cancer Core [CA 10815]
- Commonwealth Universal Research Enhancement Program, Pennsylvania Department of Health
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In the phase IIb STEP trial an HIV-1 vaccine based on adenovirus (Ad) vectors of the human serotype 5 (AdHu5) not only failed to induce protection but also increased susceptibility to HIV-1 infection in individuals with preexisting neutralizing Abs against AdHu5. The mechanisms underlying the increased HIV-1 acquisition rates have not yet been elucidated. Furthermore, it remains unclear if the lack of the vaccine's efficacy reflects a failure of the concept of T cell-mediated protection against HIV-1 or a product failure of the vaccine. Here, we compared two vaccine regimens based on sequential use of AdHu5 vectors or two different chimpanzee-derived Ad vectors in rhesus macaques that were AdHu5 seropositive or seronegative at the onset of vaccination. Our results show that heterologous booster immunizations with the chimpanzee-derived Ad vectors induced higher T and B cell responses than did repeated immunizations with the AdHu5 vector, especially in AdHu5-preexposed macaques. The Journal of Immunology, 2009, 182: 6587-6599.
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