IMMUNOGENICITY OF MALARIA VACCINES IN RHESUS MACAQUES

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This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. The subproject and investigator (PI) may have received primary funding from another NIH source, and thus could be represented in other CRISP entries. The institution listed is for the Center, which is not necessarily the institution for the investigator. Objective: To test a candidate malaria vaccine in non-human primates to identify possible adverse side effects before initializing clinical trials. Dr. David Watkins is the leader on this project. New vaccines are urgently needed against malaria to control the huge global mortality caused by this infectious disease. Scientists at the University of Oxford are developing and assessing a variety of novel approaches to improving the strength of the immune responses produced by recombinant viral vectored vaccines. The studies so far have been conducted in small animal models, but the investigators intend to proceed towards clinical trials. Therefore the goal of the present project was to vaccinate Rhesus macaques with three of the best vaccine candidates that were selected during experiments using mice. In the present non-human primate experiments we quantified the elicited immune responses, and were looking for emerging adverse reactions. The three vaccines that were studied were Adenovirus-based vaccine systems. One vaccine was made of a recombinant Adenovirus (AdCh63) and a recombinant Modified Vaccinia Ankara (MVA), each containing the malaria antigens called Me-TRAP (Multiple Epitopes conjugated to Thrombospondin Related Adhesion Protein). The second vaccine was made of a recombinant Adenovirus containing the malaria antigen (AdCh63-MeTRAP) and a recombinant Adenovirus containing a different malaria antigen called Apical Membrane Antigen-1 (AdCh63-AMA-1). The third vaccine was made of a recombinant Adenovirus containing the malaria antigens (AdCh63-MeTRAP) and a recombinant Adenovirus containing an immnoadjuvant protein from the Toll receptor signaling pathway called TRAM (AdCh63-TRAM). These composite vaccines show improved immunogenicity in mouse models as compared to a control vaccine (recombinant Adenovirus expressing the malaria antigen but no adjuvant). We investigated the safety and immunogenicity of these adenovirus vaccine system in non-human primates. PROJECT PROGRESS: The project was completed in November of 2009. This research used Animal Services and Research Services.