Vaccination with purified, cryopreserved, infectious Plasmodium vivax sporozoites

DESCRIPTION (provided by applicant): Plasmodium vivax (Pv) is the 2nd most important human malaria parasite, causing gt 80 million cases annually. However, efforts to prevent and control Pv malaria face major challenges of drug resistance and repeated relapses from dormant forms. Moreover, Pv vaccine development has been impeded, because Pv parasites cannot be grown in continuous in vitro culture. Having manufactured the only purified, cryopreserved, vialed P. vivax (Pv) sporozoites (SPZ) in the world, andshowed that these cryopreserved PvSPZ can be used to infect a chimpanzee and to infect hepatocytes in vitro, Sanaria is now poised to use these infectious PvSPZ as a first- ever whole parasite vaccine against Pv. The strategy capitalizes on the success ofone of only two approaches that have ever induced long-lasting immunity against Pf malaria in humans, one using radiation-attenuated and the other using non-attenuated fully infectious SPZ with chloroquine. In a seminal paper it was shown that immunizationby the bite of mosquitoes carrying fully infectious Plasmodium falciparum sporozoites (PfSPZ) of volunteers taking chloroquine induced 100% protective immunity, and protection was still present at 28 months after last immunization. Sanaria's unique technology platform has allowed an immediate translation of this observation with the manufacture of cryopreserved infectious PfSPZ (PfSPZ Challenge) that are fully infectious when administered by needle and syringe to humans, and trials involving infectious PfSPZ with chloroquine (PfSPZ CVac) are expected to begin in the U.S. and Europe in 2012. Conducting clinical trials of PvSPZ-CVac will require investment in development of a unique GMP manufacturing for PvSPZ. Prior to investing in such development, it wouldbe useful to obtain proof of concept data for PvSPZ-CVac in an animal model. This can only be done in non-human primates, as PvSPZ do not infect any other animals. Therefore, before manufacturing cGMP-compliant material for clinical trials, we propose toassess the protective efficacy in Saimiri boliviensis monkeys of PvSPZ-CVac. We will first establish a minimum infective dose for cryopreserved PvSPZ and subsequently carry out immunogenicity and protective efficacy studies. Together the data generated will provide insight into the in vivo infectivity of our cryopreserved PvSPZ, the protective efficacy of PvSPZ-CVac, and the immune mechanisms of protection. They will potentially provide an immune correlate of protection that can be used in humans, and inform better design of an immunization regimen for a PvSPZ vaccine for humans. PUBLIC HEALTH RELEVANCE: Plasmodium vivax (Pv) is the 2nd most important human malaria parasite, causing gt 80 million cases annually. However, efforts to prevent and control Pv malaria face major challenges of drug resistance and repeated relapses from dormant forms. Moreover, Pv vaccine development has been impeded, because Pv parasites cannot be grown in continuous in vitro culture. Having manufactured the only purified,cryopreserved, vialed P. vivax (Pv) SPZ in the world, and showing that these cryopreserved PvSPZ can be used to infect a chimpanzee and to infect hepatocytes in vitro Sanaria is now poised to use these infectious PvSPZ as a first-ever whole parasite vaccine against Pv given with chloroquine prophylaxis. Before manufacturing cGMP-compliant material for clinical trials, we propose to establish proof of principle for the PvSPZ-chloroquine model in non- human primates under specific aims designed to first establish a minimum infective dose for cryopreserved PvSPZ in Saimiri boliviensis monkeys, and subsequently carry out immunogenicity and protective efficacy studies all of which are expected to inform the subsequent first clinical trials of a whole PvSPZ vaccine.