Development of animal model for novel transmission-blocking vaccine research using gamete surface proteins of Plasmodium yoelii.

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Transmission-blocking vaccines (TBV) are being developed to interrupt malaria transmission in the mosquito vector. In principle, TBVs can be applied as follows : (1)for regional elimination of malana ; and (2) protection of other vaccines or drugs against the spread of resistant parasites. Most leading malaria transmission-blocking vaccine candidate antigens are surface proteins expressed on zygotes and ookinetes of the malaria parasites. These elicit potent transmission-blocking activity tested by using membrane-feeding apparatus. However, the transmission-blocking activity obtained from the membrane-feeding experiment may not reflect the in vivo efficacy. To answer this question, we need to establish animal model system. To identify a novel TBV candidate, we have developed a panel of monoclonal antibodies (mAb), which recognize gametocytes. Passive transfer of the mAb to mice did not confer any transmission-blocking immunity as evidenced by the inhibition of oocyst development in mos … More quito midguts. Then, to investigate whether mucosal vaccines against malaria parasite ookinete surface proteins are a viable strategy for the induction of systemic transmission-blocking immunity, the yeast-synthesized Pys25 protein was administered to mice via nasal routes in combination with cholera toxin (CT), a potent mucosal adjuvant. Intranasal administrations of Pys25 in the presence of CT induced strong systemic humoral immune responses as evidenced by high levels of serum IgG antibodies. When mice vaccinated with Pys25/CT were infected with a lethal strain of Plasmodium yoelii 17X, followed by allowing Anopheles stephensi mosquitoes to feed on their blood meals, we found that oocyst development in mosquito midguts was completely inhibited in all engorged mosquitoes examined. These results suggest that mucosal vaccines against malaria ookinete surface proteins are a feasible strategy for the induction of effective systemic humoral transmission-blocking immunity; therefore, mouse/rodent malaria system is a useful tool for the TBV study. Less