STRATEGY FOR DEVELOPMENT OF A PREERYTHROCYTIC PLASMODIUM-FALCIPARUM DNA VACCINE FOR HUMAN USE

Data generated in the Plasmodium yoelii rodent model indicated that pl asmid DNA vaccines encoding the P. yoelii circumsporozoite protein (Py CSP) or 17 kDa hepatocyte erythrocyte protein (PyHEP17) were potent in ducers of protective CD8(+) T cell responses directed against infected hepatocytes. Immunization with a mixture of these plasmids circumvent ed the genetic restriction of protective immunity and induced additive protection. A third DNA vaccine encoding the P. yoelii sporozoite sur face protein 2 (PySSP2) also induced protection. The P. falciparum gen es encoding the homologues of these three protective P. yoelii antigen s as well as another P. falciparum gene encoding a protein that is exp ressed in infected hepatocytes have been chosen for the development of a human vaccine. The optimal plasmid constructs for human use will be selected on the basis of immunogenicity data generated in mice and no nhuman primates. We anticipate that optimization of multi-gene P. falc iparum DNA vaccines designed to protect against malaria by inducing CD 8(+) cells that target infected hepatocytes will require extensive cli nical trials during the coming years. Published by Elsevier Science Lt d.