Duffy Patrick E
Am J Trop Med Hyg. 2022 Jul 11. doi: 10.4269/ajtmh.21-1337.
Among the Plasmodium falciparum surface antigens reported by Richard Carter and his colleagues decades ago, Pfs230 is currently the target of the most advanced candidate for a malaria transmission-blocking vaccine. First identified by its orthologue in the avian malaria parasite Plasmodium gallinaceum, the large cysteine-rich 14-domain Pfs230 antigen is displayed on the surface of gametes that emerge in the mosquito midgut. Gametes lacking Pfs230 cannot bind to red blood cells nor develop further into oocysts. Human antibodies against Pfs230 lyse gametes in the presence of complement, which largely explains serum transmission-blocking activity in Pfs230 antisera. A protein-protein conjugate vaccine that incorporates the first domain of the Pfs230 antigen induced greater serum transmission-reducing activity versus a similarly manufactured Pfs25 vaccine in U.S. trials, and is currently in phase II field trials in Mali.
几十年前理查德·卡特及其同事报告的恶性疟原虫表面抗原中，Pfs230目前是疟疾传播阻断疫苗最先进候选物的靶点。这种富含半胱氨酸的14结构域的大型Pfs230抗原最初是通过其在禽疟原虫鸡疟原虫中的同源物鉴定出来的，它展示在蚊子中肠出现的配子表面。缺乏Pfs230的配子既不能与红细胞结合，也不能进一步发育成卵囊。针对Pfs230的人类抗体在补体存在的情况下会裂解配子，这在很大程度上解释了Pfs230抗血清中的血清传播阻断活性。在美国的试验中，一种包含Pfs230抗原第一结构域的蛋白质-蛋白质偶联疫苗相对于同样制造的Pfs25疫苗诱导出了更强的血清传播减少活性，目前正在马里进行II期现场试验。
