CIRCUMVENTING GENETIC RESTRICTION OF PROTECTION AGAINST MALARIA WITH MULTIGENE DNA IMMUNIZATION - CD8(-CELL-DEPENDENT, INTERFERON-GAMMA-DEPENDENT, AND NITRIC-OXIDE-DEPENDENT IMMUNITY() T)

Despite efforts to develop vaccines that protect against malaria by in ducing CD8(+) T cells that kill infected hepatocytes, no subunit vacci ne has been shown to circumvent the genetic restriction inherent in th is approach, and little is known about the interaction of subunit vacc ine-induced immune effectors and infected hepatocytes. We now report t hat immunization with plasmid DNA encoding the Plasmodium yoelii circu msporozoite protein protected one od five strains of mice against mala ria (H-2(d), 75%); a PyHEP17 DNA vaccine protected three of the five s trains (H-2(a), 71%; H-2(k), 54%; H-2(d), 26%); and the combination pr otected 82% of H-2(a), 90% of H-2(k), and 88% of H-2(d) mice. Protecti on was absolutely dependent on CD8(+) T cells, IFN-gamma, or nitric ox ide. These data introduce a new target of protective preerythrocytic i mmune responses, PyHEP17 and its P. falciparum homologue, and provide a realistic perspective on the opportunities and challenges inherent i n developing malaria vaccines that target the infected hepatocyte.