期刊
VACCINE
卷 30, 期 21, 页码 3188-3195出版社
ELSEVIER SCI LTD
DOI: 10.1016/j.vaccine.2012.03.001
关键词
HIV-1 vaccine; Pathogenic SHIV; Non-human primate; Envelope cocktail; Ultra violet-inactived vaccinia virus
资金
- NIH NCI Cancer Center [P30-CA21765]
- NIH-NIAID [P01 AI45142, R21-AI56974, R01 AI078819]
- NIH NCRR [P51-RR00164]
- Aboussie Fund
- Federated Department Stores
- Mitchell Fund
- Carl C. Anderson Sr. and Marie Joe Anderson Charitable Foundation
- James B. Pendleton Charitable Trust
- Pioneer Fund
- American Lebanese Syrian-Associated Charities (ALSAC)
The pandemic of HIV-1 has continued for decades, yet there remains no licensed vaccine. Previous research has demonstrated the effectiveness of a multi-envelope, multi-vectored HIV-1 vaccine in a macaque-SHIV model, illustrating a potential means of combating HIV-1. Specifically, recombinant DNA, vaccinia virus (VV) and purified protein (DVP) delivery systems were used to vaccinate animals with dozens of antigenically distinct HIV-1 envelopes for induction of immune breadth. The vaccinated animals controlled disease following challenge with a heterologous SHIV. This demonstration suggested that the antigenic cocktail vaccine strategy, which has succeeded in several other vaccine fields (e.g. pneumococcus), might also succeed against HIV-1. The strategy remains untested in an advanced clinical study, in part due to safety concerns associated with the use of replication-competent VV. To address this concern, we designed a macaque study in which psoralen/ultraviolet light-inactivated W (UV VV) was substituted for replication-competent W in the multi-envelope DVP protocol. Control animals received a vaccine encompassing no VV, or no vaccine. All W vaccinated animals generated an immune response toward W, and all vaccinated animals generated an immune response toward HIV-1 envelope. After challenge with heterologous SHIV 89.6P, animals that received replication-competent W or UV W experienced similar outcomes. They exhibited reduced peak viral loads, maintenance of CD4+ T cell counts and improved survival compared to control animals that received no VV or no vaccine; there were 0/15 deaths among all animals that received VV and 5/9 deaths among controls. Results define a practical means of improving W safety, and encourage advancement of a promising multi-envelope DVP HIV-1 vaccine candidate. (C) 2012 Elsevier Ltd. All rights reserved.
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