The acquired immunodeficiency syndrome (AIDS) caused by HlV-1 is the fourth leading cause of death woridwide. Development of an effective vaccine against HIV/AIDS is the long term solution to this problem. The failure of Merck's adenovirus type 5 (Ad5) based HIV-1 clade B vaccine in humans that is designed to elicit primarily antiviral T cells strongly suggests the need to develop novel vaccine approaches that generate high levels of anti-viral T cells with improved function as well as protective Ab. The goal of this HIVRAD is to generate high levels of broadiv cross-reactive antiviral T cells witii enhanced proliferative/protective phenotvpe and high aviditv antiviral binding Ab bv targeting CD40 and mTOR (mammalian target of rapamycin) pathwavs. The overall objectives for this Core are to provide the required experimental animals and support services needed to facilitate the AIDS vaccine development studies proposed in projects 1 and 2. This will be accomplished by the following specific aims: 1. To provide the required 2 to 3 year old rhesus macaques as outiined in projects 1 and 2 of this application. 2. To immunize the experimental animals as specified in projects 1 &2. 3. To test the safety, optimization of dose and efficacy of mTOR inhibitor (rapamycin) in experimental animals as described in project 2. 4. To evaluate the efficacy of DNA/MVA-SIV vaccines following an intrarectal SIV251 challenge as specified in projects 1 and 2. 5. To monitor the experimental animals on a daily basis to assess their clinical condition. 6. To perform periodic physical examinations and blood collections from the experimental animals to assess the animal's physical condition and to provide specimens for laboratory evaluations as detailed in projects 1 and 2. 7. To perfonn hemogram, blood chemistry and flow cytometry evaluations to document any changes in the blood cell counts and determine percent and absolute numbers of T cells, B cells and T-cell subsets following immunizations. 8. To perform complete gross and histologic evaluation of any experimental animals that die during the course of the study.
WHO estimates that there are currently 32 million humans living with HIV/AIDS. Drugs and improved treatment regimens have successfully prolonged the lives of infected individuals in first world countries. However, these are not affordable for the vast majority of HIV-infected individuals. Even in developed nations these are limited by toxicity, affordability, the need for rigorous adherence to therapy and the emergence of drug resistant viruses. Thus, there is a great need to develop a safe and effective HIV vaccine that provides a low-cost, lowtoxicity solution to long-term control of viral replication - the main goal of this PPG.
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