PLASMODIUM-YOELII - 17-KDA HEPATIC AND ERYTHROCYTIC STAGE PROTEIN IS THE TARGET OF AN INHIBITORY MONOCLONAL-ANTIBODY

Infected hepatocytes are important targets for malaria vaccines. To id entify Plasmodium yoelii proteins expressed in infected hepatocytes, w e immunized BALB/c ByJ mice with P. yoelii liver stage schizonts and p roduced a panel of monoclonal antibodies (Mabs). An IgG1 Mab, navy yoe lii liver stage 3 (NYLS3), had the strongest reactivity against liver stage parasites and was selected for further characterization. The Mab does not recognize P. yoelii sporozoites, but recognizes liver stages parasites within 6 hr of invasion of mouse hepatocytes and throughout the hepatic and asexual erythrocytic stages of the parasite life cycl e as determined by the immunofluorescent antibody test. This Mab is sp ecies-specific, and it reacts with liver stages of P. yoelii but does not react with liver stages of other Plasmodium species. The protein r ecognized by this Mab is present on the parasitophorous vacuole membra ne of infected hepatocytes and erythrocytes as demonstrated by immunoe lectron microscopy and has a relative molecular weight of 17 kDa as de monstrated by immunoblot of an extract of infected erythrocytes. It is therefore designated P. yoelii hepatic and erythrocytic stage protein , 17 kDa or PyHEP17. When added to primary cultures of mouse hepatocyt es 24 hr after inoculation with P. yoelii sporozoites, when all sporoz oites have invaded hepatocytes, NYLS3 eliminates up to 98% of liver-st age parasites. Intravenous injection of NYLS3 into mice delays the ons et and reduces the density of blood-stage parasitemia after sporozoite or blood-stage challenge. The P. falciparum and P. vivax homologs of PyHEP17 may therefore be important targets for vaccines designed to at tack the hepatic and erythrocytic stages of the parasite life cycle. ( C) 1995 Academic Press, Inc.