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. 2022 Dec;612(7940):534-539.
doi: 10.1038/s41586-022-05466-7. Epub 2022 Dec 7.

In vitro production of infectious Plasmodium falciparum sporozoites

Abraham G Eappen  1 , Tao Li  1 , Meghan Marquette  1 , Sumana Chakravarty  1 , Natasha Kc  1   2 , Gigliola Zanghi  3 , Benjamin U Hoffman  4   5 , Hashani Hettiarachchi  1   6 , Asha Patil  1 , Yonas Abebe  1 , Christiane Tran  1 , Alemtaye A Yossef  1 , Ian McWilliams  1 , Robert D Morrison  3 , Ayyappan Rathakrishnan  1 , Ehud Inbar  1 , Ahmed S I Aly  1 , Patricia De La Vega  1 , Maria Belmonte  7   8 , Martha Sedegah  7 , Tint Wai  1   2 , Joseph J Campo  9 , Harley King  10 , Stefan H I Kappe  3   11   12 , MingLin Li  1   2 , Peter F Billingsley  1 , B Kim Lee Sim  1   2 , Stephen L Hoffman  13
Affiliations

In vitro production of infectious Plasmodium falciparum sporozoites

Abraham G Eappen et al. Nature. 2022 Dec.

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)1-7. 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.

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References

    1. Hoffman, S. L. et al. Development of a metabolically active, non-replicating sporozoite vaccine to prevent Plasmodium falciparum malaria. Hum. Vaccin. 6, 97–106 (2010). - DOI
    1. Seder, R. A. et al. Protection against malaria by intravenous immunization with a nonreplicating sporozoite vaccine. Science 341, 1359–1365 (2013). - DOI
    1. Epstein, J. E. et al. Protection against Plasmodium falciparum malaria by PfSPZ vaccine. JCI Insight 2, e89154 (2017). - DOI
    1. Mordmuller, B. et al. Sterile protection against human malaria by chemoattenuated PfSPZ vaccine. Nature 542, 445–449 (2017). - DOI
    1. Jongo, S. A. et al. Increase of dose associated with decrease in protection against controlled human malaria infection by PfSPZ vaccine in Tanzanian adults. Clin. Infect. Dis. 71, 2849–2857 (2020). - DOI

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