Aotus lemunnus is currently accepted to be one of the most appropriate animal models for human malaria parasite infection (1-3). This species is susceptible to infection by P. falciparum (4-6), P. vivax (2, 7-10) and P. malariae (11-12)and unlike chimpanzees, it is available in sufficient numbers to carry out studies with adequate sample sizes. Based on this susceptibility, the model has been extensively used to study the immunogenicity and protective efficacy of malaria vaccine candidates. However, during the past several years there has been concern that monkey models may not reproduce the immune response of humans to specific antigens, leading to results in pre-clinical trials that do not predict the outcome in humans. Despite this concern, we have conducted an important number of pre-clinical trials using this primate model during the last decade, and the results of many of our studies suggest that the Aotus model is a reliable system for testing the immunogenicity and protective efficacy of candidate malaria vaccines. Thus we propose that the Aotus model has the potential to play a critical role in malaria vaccine development, and for this reason, we plan to conduct systematic analyses in order to validate the model. These analyses are the subject of project 3. We plan to approach this issue by studying the response of Aotus monkeys to different P. vivax candidate antigens and vaccine formulations, and compare these to the responses induced in humans exposed to P. vivax through immunizations with irradiated sporozoites (project 2), or exposed to the parasite under natural conditions or immunized with candidate vaccines by ourselves and by our collaborators (not part of this proposal). This project will cover analyses of both preerythrocytic and erythrocytic asexual stage antigens available from different collaborators. We will use different fragments of the P. vivax CSP and SSP-2, as well as different regions of the MSP-1 and the DBP. The response of Aotus monkeys to different parasite antigens and gene constructs will be determined.