小柯机器人

美国Sanaria公司Stephen L. Hoffman研究组实现传染性恶性疟原虫孢子体的体外生产。相关论文于2022年12月7日在线发表在《自然》杂志上。

研究人员表示，为了预防和消除疟疾，目前需要一种有效的疫苗。已经证明对人类疟疾具有90%以上保护效力的唯一免疫原是由蚊子制造的恶性疟原虫孢子体（mPfSPZ）。在没有蚊子的情况下，在体外生产PfSPZ（iPfSPZ）的能力将大大增强PfSPZ疫苗的生产和蚊子阶段的疟疾研究，但这种能力是缺乏的。

研究人员报告了数以亿计iPfSPZ的生产情况。iPfSPZ在培养中侵入人类肝细胞，并发育成表达恶性疟原虫表面蛋白1（PfMSP1）的成熟肝阶段裂殖体，其数量与mPfSPZ相当。当注射到含有人源化肝脏的FRGhuHep小鼠体内时，iPfSPZ侵入人类肝细胞并发育成表达PfMSP1的肝脏晚期寄生虫，其数量为冷冻保存的mPfSPZ的45%。感染了iPfSPZ的FRGhuHep小鼠的人血在培养中产生了无性和有性红细胞阶段的寄生虫，配子细胞在喂给蚊子时发育成PfSPZ，在没有蚊子或灵长类动物的情况下完成了恶性疟原虫从感染性配子细胞到感染性配子细胞的生命周期。

附：英文原文

Title: In vitro production of infectious Plasmodium falciparum sporozoites

Author: 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.

Issue&Volume: 2022-12-07

Abstract: 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.

DOI: 10.1038/s41586-022-05466-7

Source: https://www.nature.com/articles/s41586-022-05466-7

Nature：《自然》，创刊于1869年。隶属于施普林格·自然出版集团，最新IF：69.504
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