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. 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 intend to proceed towards clinical trials with these promising new adjuvanted vaccines. However, before initializing clinical trials it is mandatory to test the candidate vaccines in non-human primates to identify possible adverse side effects. Therefore the goal of the present project is to vaccinate Rhesus macaques with the best vaccine candidate that was selected during experiments using mice. In the present non-human primate experiments we will quantify the elicited immune responses, and will be looking for emerging adverse reactions. Each animal will be immunized (day 0) with a replication-deficient Adenovirus vector (AdCh63) genetically engineered to express a fusion malaria antigen ME-TRAP (Multiple Epitope-Thrombospondin Related Adhesion Protein). The animals will be boosted at least 8 weeks later with a highly attenuated pox-virus (MVA) also expressing ME-TRAP. The adjuvanted vectors also express a molecular adjuvant derived from a family of human co-stimulatory molecules and cytokines.