Plasmodium yoelii:17-kDa Hepatic and Erythrocytic Stage Protein Is the Target of an Inhibitory Monoclonal Antibody

Autor: Charoenvit, Y., Mellouk, S., Sedegah, M., Toyoshima, T., Leef, M.F., Delavega, P., Beaudoin, R.L., Aikawa, M., Fallarme, V., Hoffman, S.L.
Zdroj: Experimental Parasitology; May 1995, Vol. 80 Issue: 3 p419-429, 11p
Abstrakt: Infected hepatocytes are important targets for malaria vaccines. To identify Plasmodium yoeliiproteins expressed in infected hepatocytes, we immunized BALB/c ByJ mice with P. yoeliiliver stage schizonts and produced a panel of monoclonal antibodies (Mabs). An IgG1 Mab, navy yoeliiliver stage 3 (NYLS3), had the strongest reactivity against liver stage parasites and was selected for further characterization. The Mab does not recognize P. yoeliisporozoites, 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 cycle as determined by the immunofluorescent antibody test. This Mab is species-specific, and it reacts with liver stages of P. yoeliibut does not react with liver stages of other Plasmodiumspecies. The protein recognized by this Mab is present on the parasitophorous vacuole membrane of infected hepatocytes and erythrocytes as demonstrated by immunoelectron microscopy and has a relative molecular weight of 17 kDa as demonstrated by immunoblot of an extract of infected erythrocytes. It is therefore designated P. yoeliihepatic and erythrocytic stage protein, 17 kDa or PyHEP17. When added to primary cultures of mouse hepatocytes 24 hr after inoculation with P. yoeliisporozoites, when all sporozoites have invaded hepatocytes, NYLS3 eliminates up to 98% of liver-stage parasites. Intravenous injection of NYLS3 into mice delays the onset and reduces the density of blood-stage parasitemia after sporozoite or blood-stage challenge. The P. falciparumand P. vivaxhomologs of PyHEP17 may therefore be important targets for vaccines designed to attack the hepatic and erythrocytic stages of the parasite life cycle.
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