Circumventing Genetic Restriction of Protection against Malaria with MultigeneDNA Immunization: CD8+ T Cell-, Inteferon and Nitric Oxide-Dependent Immunity

摘要

Despite efforts to develop vaccines that protect against malaria by inducing CD8+T cells that kill infected hepatocytes, no subunit vaccine has been shown to circumvent the genetic restriction inherent in this approach, and little is known about the interaction of subunit vaccine induced immune effectors and infected hepatocytes. We now report that immunization with plasmid DNA encoding the-Plasmodium yoelii circumsporozoite protein protected one of five strains of mice against malaria (H-2d, 75%) a PyHEP17 DNA vaccine protected three of the five strains (H-2%, 71%; H-2k, 54%; H-2d, 26%); and the combination protected 82% of H-2a, 90% of H-2k, and 88% of H-2d mice. Protection was absolutely dependent on CD8+ T cells, IFN-gamma, or nitric oxide. These data introduce a new target of protective preerythrocytic immune responses, PyHEP17 and its P. falciparum homologue, and provide a realistic perspective on the opportunities and challenges inherent in developing malaria vaccines that target the infected hepatocyte.