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Secreted HSP Vaccine for Malaria Prophylaxis

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Technical Report,30 Sep 2014,29 Sep 2015

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University of Miami Coral Gables United States

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Proposed vaccine principle relies on secreted gp96-lg chaperoning PfCSP and PfAMA 1 sporozoite proteins that are efficiently taken up and cross presented by activated DC via MHC I to CD8 CTL, thereby stimulating an avid, antigen specific, cytotoxic T cell response . This vaccine principle has been used successfully in murine models of cancer, in non-human primates for SIV vaccination and is in clinical trials for the treatment of non-small cell lung cancer patients. The generation of a powerful, cytotoxicanti sporozoite CD8 CTL response by the vaccine is expected to provide prophylactic immunity for malaria by removing infected liver cells before sporozoites can replicate and spread to the erythrocyte stage causing parasitemia. In the second year , we performed and completed all mouse immunogenicity experiments that addressed the effect of primary 293-gp96-lg PfAMA 1-PfCSP immunization as well as effect of different route of immunization on the gp96-induced immunogenicity. We found that gp96 delivered subcutaneously, induces very strong antigen specific immune response systemically as well as liver-infiltrating effector CD8 T cells. We have also started manufacturing GMP-grade vaccine material for use in non-human primate studies.

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