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Secreted HSP Vaccine for Malaria Prophylaxis

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Annual rept. 30 Sep 2013-29 Sep 2014

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Proposed vaccine principle relies on secreted gp96 - Ig chaperoning PfCSP and PfAMA1 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, cytotoxic anti 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. We establish collaboration with NMRC to design the vaccine cell lines. NMRC provided plasmid vectors carrying the PfAMA1 and PfCSP transgenes. We generated 293 - gp96 - Ig - PfAMA1 - PfCSP cells by co-transfecting 293 cells with gp96-Ig, PfAMA1 and PfCSP. Completion of the 293-gp96-IgPfAMA1-PfCSP vaccine cell lines serves as the initial go, no-go milestone for this application. We reached this milestone within the first year of the grant period, as it was proposed in SOW. We are currently expanding vaccine cells in order to proceed to proposed immunogenicity studies in mouse model.

Subject Categories:

  • Biochemistry
  • Anatomy and Physiology
  • Medicine and Medical Research

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