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Plasmodium falciparum 7G8 challenge provides conservative prediction of efficacy of PfNF54-based PfSPZ Vaccine in Africa

Author

Listed:
  • Joana C. Silva

    (University of Maryland School of Medicine
    University of Maryland School of Medicine)

  • Ankit Dwivedi

    (University of Maryland School of Medicine)

  • Kara A. Moser

    (University of Maryland School of Medicine)

  • Mahamadou S. Sissoko

    (University of Science, Techniques and Technologies of Bamako)

  • Judith E. Epstein

    (Naval Medical Research Center)

  • Sara A. Healy

    (Laboratory of Malaria Immunology and Vaccinology, NIAID, NIH)

  • Kirsten E. Lyke

    (Center for Vaccine Development and Global Health, University of Maryland School of Medicine)

  • Benjamin Mordmüller

    (University of Tübingen and German Center for Infection Research
    Centre de Recherches Médicales de Lambaréné
    Radboud University Medical Center)

  • Peter G. Kremsner

    (University of Tübingen and German Center for Infection Research
    Centre de Recherches Médicales de Lambaréné)

  • Patrick E. Duffy

    (Laboratory of Malaria Immunology and Vaccinology, NIAID, NIH)

  • Tooba Murshedkar

    (Sanaria Inc.)

  • B. Kim Lee Sim

    (Sanaria Inc.)

  • Thomas L. Richie

    (Sanaria Inc.)

  • Stephen L. Hoffman

    (Sanaria Inc.)

Abstract

Controlled human malaria infection (CHMI) has supported Plasmodium falciparum (Pf) malaria vaccine development by providing preliminary estimates of vaccine efficacy (VE). Because CHMIs generally use Pf strains similar to vaccine strains, VE against antigenically heterogeneous Pf in the field has been required to establish VE. We increased the stringency of CHMI by selecting a Brazilian isolate, Pf7G8, which is genetically distant from the West African parasite (PfNF54) in our PfSPZ vaccines. Using two regimens to identically immunize US and Malian adults, VE over 24 weeks in the field was as good as or better than VE against CHMI at 24 weeks in the US. To explain this finding, here we quantify differences in the genome, proteome, and predicted CD8 T cell epitopes of PfNF54 relative to 704 Pf isolates from Africa and Pf7G8. We show that Pf7G8 is more distant from PfNF54 than any African isolates tested. We propose VE against Pf7G8 CHMI for providing pivotal data for malaria vaccine licensure for travelers to Africa, and potentially for endemic populations, because the genetic distance of Pf7G8 from the Pf vaccine strain makes it a stringent surrogate for Pf parasites in Africa.

Suggested Citation

  • Joana C. Silva & Ankit Dwivedi & Kara A. Moser & Mahamadou S. Sissoko & Judith E. Epstein & Sara A. Healy & Kirsten E. Lyke & Benjamin Mordmüller & Peter G. Kremsner & Patrick E. Duffy & Tooba Murshed, 2022. "Plasmodium falciparum 7G8 challenge provides conservative prediction of efficacy of PfNF54-based PfSPZ Vaccine in Africa," Nature Communications, Nature, vol. 13(1), pages 1-9, December.
    • Handle: RePEc:nat:natcom:v:13:y:2022:i:1:d:10.1038_s41467-022-30882-8
    DOI: 10.1038/s41467-022-30882-8
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    References listed on IDEAS

    as
    1. Agnes Mwakingwe-Omari & Sara A. Healy & Jacquelyn Lane & David M. Cook & Sahand Kalhori & Charles Wyatt & Aarti Kolluri & Omely Marte-Salcedo & Alemush Imeru & Martha Nason & Lei K. Ding & Hope Decede, 2021. "Two chemoattenuated PfSPZ malaria vaccines induce sterile hepatic immunity," Nature, Nature, vol. 595(7866), pages 289-294, July.
    2. Zita Sulyok & Rolf Fendel & Bianca Eder & Freia-Raphaella Lorenz & Natasha KC & Matthias Karnahl & Albert Lalremruata & The T. Nguyen & Jana Held & Folashade Almeine Cyntiche Adjadi & Torsten Klockenb, 2021. "Heterologous protection against malaria by a simple chemoattenuated PfSPZ vaccine regimen in a randomized trial," Nature Communications, Nature, vol. 12(1), pages 1-10, December.
    3. Benjamin Mordmüller & Güzin Surat & Heimo Lagler & Sumana Chakravarty & Andrew S. Ishizuka & Albert Lalremruata & Markus Gmeiner & Joseph J. Campo & Meral Esen & Adam J. Ruben & Jana Held & Carlos Lam, 2017. "Sterile protection against human malaria by chemoattenuated PfSPZ vaccine," Nature, Nature, vol. 542(7642), pages 445-449, February.
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