In vitro production of infectious Plasmodium falciparum sporozoites

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 A. Yossef, Ian McWilliams, Robert D. Morrison, Ayyappan Rathakrishnan, Ehud Inbar, Ahmed S. I. Aly, Patricia Vega, Maria Belmonte, Martha Sedegah, Tint Wai, Joseph J. Campo, Harley King, Stefan H. I. Kappe, MingLin Li, Peter F. Billingsley, B. Kim Lee Sim and Stephen L. Hoffman ()
Additional contact information
Abraham G. Eappen: Sanaria
Tao Li: Sanaria
Meghan Marquette: Sanaria
Sumana Chakravarty: Sanaria
Natasha Kc: Sanaria
Gigliola Zanghi: Seattle Children’s Research Institute
Benjamin U. Hoffman: Columbia University Irving Medical Center
Hashani Hettiarachchi: Sanaria
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
Martha Sedegah: Naval Medical Research Center
Tint Wai: Sanaria
Joseph J. Campo: Antigen Discovery Incorporated (ADI)
Harley King: Institute for Bioscience and Biotechnology Research
Stefan H. I. Kappe: Seattle Children’s Research Institute
MingLin Li: Sanaria
Peter F. Billingsley: Sanaria
B. Kim Lee Sim: Sanaria
Stephen L. Hoffman: Sanaria

Nature, 2022, vol. 612, issue 7940, 534-539

Abstract: 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.

Date: 2022
References: Add references at CitEc
Citations:

Downloads: (external link)
https://www.nature.com/articles/s41586-022-05466-7 Abstract (text/html)
Access to the full text of the articles in this series is restricted.

Related works:
This item may be available elsewhere in EconPapers: Search for items with the same title.

Export reference: BibTeX RIS (EndNote, ProCite, RefMan) HTML/Text

Persistent link: https://EconPapers.repec.org/RePEc:nat:nature:v:612:y:2022:i:7940:d:10.1038_s41586-022-05466-7

Ordering information: This journal article can be ordered from
https://www.nature.com/

DOI: 10.1038/s41586-022-05466-7

Access Statistics for this article

Nature is currently edited by Magdalena Skipper

More articles in Nature from Nature
Bibliographic data for series maintained by Sonal Shukla () and Springer Nature Abstracting and Indexing ().