Nature:体外生成传染性恶性疟原虫孢子
In vitro production of infectious Plasmodium falciparum sporozoites
作者:Eappen, Abraham G., Li, Tao, Marquette, Meghan, Chakravarty, Sumana, KC, Natasha, Zanghi, Gigliola, Hoffman, Benjamin U., Hettiarachchi, Hashani, Patil, Asha, Abebe, Yonas, Tran, Christiane, Yossef, Alemtaye A., McWilliams, Ian, Morrison, Robert D., Rathakrishnan, Ayyappan, Inbar, Ehud, Aly, Ahmed S. I., De La Vega, Patricia, Belmonte, Maria, Sedegah, Martha, Wai, Tint, Campo, Joseph J., King, Harley, Kappe, Stefan H. I., Li, MingLin, Billingsley, Peter F., Sim, B. Kim Lee, Hoffman, Stephen L.
Nature:2022/12/07
An effective vaccine is needed for the prevention and elimination of malaria. The only immunogens that have been shown to have a protective efficacy of more than 90% against human malaria are Plasmodium falciparum (Pf) sporozoites (PfSPZ) manufactured in mosquitoes (mPfSPZ)1,2,3,4,5,6,7. The ability to produce PfSPZ in vitro (iPfSPZ) without mosquitoes would substantially enhance the production of PfSPZ vaccines and mosquito-stage malaria research, but this ability is lacking. Here we report the production of hundreds of millions of iPfSPZ. iPfSPZ invaded human hepatocytes in culture and developed to mature liver-stage schizonts expressing P. falciparum merozoite surface protein 1 (PfMSP1) in numbers comparable to mPfSPZ. When injected into FRGhuHep mice containing humanized livers, iPfSPZ invaded the human hepatocytes and developed to PfMSP1-expressing late liver stage parasites at 45% the quantity of cryopreserved mPfSPZ. Human blood from FRGhuHep mice infected with iPfSPZ produced asexual and sexual erythrocytic-stage parasites in culture, and gametocytes developed to PfSPZ when fed to mosquitoes, completing the P. falciparum life cycle from infectious gametocyte to infectious gametocyte without mosquitoes or primates.
目前唯一可有效预防人类疟原虫的免疫原是蚊子产生的恶性疟原虫孢子(mPFSPZ)。本研究报告在体外生成上亿个iPfSPZ,可入侵实验室培养的人类肝细胞,发育成成熟的肝阶段裂殖体表达恶性疟原虫裂殖子表面蛋白1(PfMSP1),数量与mPfSPZ相当。结果揭示了恶性疟原虫从具有传染性的配子体到无需蚊子或者灵长类动物的传染性配子体的生命周期。
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