This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. Primary support for the subproject and the subproject's principal investigator may have been provided by other sources, including other NIH sources. The Total Cost listed for the subproject likely represents the estimated amount of Center infrastructure utilized by the subproject, not direct funding provided by the NCRR grant to the subproject or subproject staff. Objective: To vaccinate Rhesus macaques with three of the best vaccine candidates selected during experiments using mice and quantify the elicited immune responses to look for emerging adverse reactions. New vaccines are urgently needed against malaria to control the huge global mortality caused by this infectious disease. Many leading candidate vaccines include a gene from these microbes as part of an attenuated virus known as a vector. Vectored vaccines, however, will need to induce strong immunity if these vaccines are to be widely successful. 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 such viral vectored vaccines. The studies so far have been conducted in small animal models, but the investigators will now proceed towards clinical trials with these promising new vaccines. However, before initializing clinical trials it is mandatory to test the candidate vaccines in non-human primates to identify possible adverse side effects. PROGRESS: Scientists at the University of Oxford had developed three Adenovirus-based vaccine systems to immunize against malaria antigens. One vaccine regimen was made of a recombinant Adenovirus (AdCh63) and a recombinant Modified Vaccinia Ankara (MVA), each containing the malaria antigens Multiple Epitopes conjugated to Thrombospondin Related Adhesion Protein (Me-TRAP). The second vaccine regimen was made of a recombinant Adenovirus containing the malaria antigens Multiple Epitopes conjugated to Thrombospondin Related Adhesion Protein (Me-TRAP), a recombinant Adenovirus containing an immunostimulatory antigen called 4-1BBL (AdCh63-4-1BBL) and a Modified Vaccinia Ankara (MVA) containing both the malaria and the immunostimulatory antigens (MVA-MeTRAP-4-1BBL). The third vaccine regimen was made of a recombinant Adenovirus containing the modified malaria antigens Multiple Epitopes conjugated to Thrombospondin Related Adhesion Protein conjugated to an immunostimulatory protein IMX313 and a recombinant MVA containing the modified malaria antigens Multiple Epitopes conjugated to Thrombospondin Related Adhesion Protein conjugated to an immunostimulatory protein IMX313. These composite vaccines had shown improved immunogenicity in mouse models as compared to a control vaccine (recombinant Adenovirus expressing the malaria antigen no immunostimulatory proteins). We investigated the safety and immunogenicity of these Adenovirus vaccine systems in non-human primates. We finished these experiments at the end of November 2010. This research used Animal Services, CPI and Immunology Services. PUBLICATIONS: None.
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