IDEAS home Printed from https://ideas.repec.org/a/nat/nature/v612y2022i7940d10.1038_s41586-022-05466-7.html
   My bibliography  Save this article

In vitro production of infectious Plasmodium falciparum sporozoites

Author

Listed:
  • Abraham G. Eappen

    (Sanaria)

  • Tao Li

    (Sanaria)

  • Meghan Marquette

    (Sanaria)

  • Sumana Chakravarty

    (Sanaria)

  • Natasha KC

    (Sanaria
    Protein Potential)

  • Gigliola Zanghi

    (Seattle Children’s Research Institute)

  • Benjamin U. Hoffman

    (Columbia University Irving Medical Center
    UCSF)

  • Hashani Hettiarachchi

    (Sanaria
    Ohio University)

  • Asha Patil

    (Sanaria)

  • Yonas Abebe

    (Sanaria)

  • Christiane Tran

    (Sanaria)

  • Alemtaye A. Yossef

    (Sanaria)

  • Ian McWilliams

    (Sanaria)

  • Robert D. Morrison

    (Seattle Children’s Research Institute)

  • Ayyappan Rathakrishnan

    (Sanaria)

  • Ehud Inbar

    (Sanaria)

  • Ahmed S. I. Aly

    (Sanaria)

  • Patricia Vega

    (Sanaria)

  • Maria Belmonte

    (Naval Medical Research Center
    Henry M. Jackson Foundation)

  • Martha Sedegah

    (Naval Medical Research Center)

  • Tint Wai

    (Sanaria
    Protein Potential)

  • Joseph J. Campo

    (Antigen Discovery Incorporated (ADI))

  • Harley King

    (Institute for Bioscience and Biotechnology Research)

  • Stefan H. I. Kappe

    (Seattle Children’s Research Institute
    University of Washington
    University of Washington)

  • MingLin Li

    (Sanaria
    Protein Potential)

  • Peter F. Billingsley

    (Sanaria)

  • B. Kim Lee Sim

    (Sanaria
    Protein Potential)

  • Stephen L. Hoffman

    (Sanaria)

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.

Suggested Citation

  • Abraham G. Eappen & Tao Li & Meghan Marquette & Sumana Chakravarty & Natasha KC & Gigliola Zanghi & Benjamin U. Hoffman & Hashani Hettiarachchi & Asha Patil & Yonas Abebe & Christiane Tran & Alemtaye , 2022. "In vitro production of infectious Plasmodium falciparum sporozoites," Nature, Nature, vol. 612(7940), pages 534-539, December.
    • Handle: RePEc:nat:nature:v:612:y:2022:i:7940:d:10.1038_s41586-022-05466-7
    DOI: 10.1038/s41586-022-05466-7
    as

    Download full text from publisher

    File URL: https://www.nature.com/articles/s41586-022-05466-7
    File Function: Abstract
    Download Restriction: Access to the full text of the articles in this series is restricted.
    File URL: https://libkey.io/10.1038/s41586-022-05466-7?utm_source=ideas
    LibKey link: if access is restricted and if your library uses this service, LibKey will redirect you to where you can use your library subscription to access this item
    ---><---

    As the access to this document is restricted, you may want to search for a different version of it.

    More about this item

    Statistics

    Access and download statistics

    Corrections

    All material on this site has been provided by the respective publishers and authors. You can help correct errors and omissions. When requesting a correction, please mention this item's handle: RePEc:nat:nature:v:612:y:2022:i:7940:d:10.1038_s41586-022-05466-7. See general information about how to correct material in RePEc.

    If you have authored this item and are not yet registered with RePEc, we encourage you to do it here. This allows to link your profile to this item. It also allows you to accept potential citations to this item that we are uncertain about.

    We have no bibliographic references for this item. You can help adding them by using this form .

    If you know of missing items citing this one, you can help us creating those links by adding the relevant references in the same way as above, for each refering item. If you are a registered author of this item, you may also want to check the "citations" tab in your RePEc Author Service profile, as there may be some citations waiting for confirmation.

    For technical questions regarding this item, or to correct its authors, title, abstract, bibliographic or download information, contact: Sonal Shukla or Springer Nature Abstracting and Indexing (email available below). General contact details of provider: http://www.nature.com .

    Please note that corrections may take a couple of weeks to filter through the various RePEc services.

    IDEAS is a RePEc service. RePEc uses bibliographic data supplied by the respective publishers.