Efficacy of the monoclonal antibodies and their mechanism of transmission-blocking activitiesof Plasmodium yoelii in Anopheles stephensi.

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The monoclonal antibodies (mAb) against Plasmodium yoelii zygote and ookinete have been shown to block infectivity of the parasites to mosquitoes. We have studied the efficacy of the mAbs and their mechanism of transmission-blocking activities. The transmission-blocking effect of mAb 4 against P.yoelii zygote/ookinete 28 kD protein (Pys28) was complete in Anopheles stephensi. Moreover, the blockade of mAb 4 was stronger than that of mAb 10 against P.yoelii zygote/ookinete 22 kD protein (Pys22). Monoclonal antibody 4 inhibited the zygote formation and mAb 10 suppressed the maturation of zygotes to ookinetes in mosquito midgut in 4-15h after blood meal. In vitro experiment showed that both 28 kD and 22 kD determinants were already present in the cytoplasm of gametocytes, and early zygotes (approx.30 min post-culture) expressed a protein of Mr 28 kD or 22 kD in their cytoplasm and synthesized on their surface for 2-24h or 4-24h post-culture respectively. The onset of surface expression of Pys28 was earlier than Pys22. Fab fragments of mAb 4 had transmission-blocking activity in mice. Fab fragments of mAb 10 did not have detectable transmission-blocking effect, although F (ab')_2 did. These data suggest that mAb 4 and mAb 10 cause suppression of oocyst development in the complement and antibody-dependent cell-mediated cytotoxicity, and that mAb 4 might prevent the function of the target surface protein.