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Development of clinical immunity to Plasmodium vivax following repeat controlled human malaria infection

Author

Listed:
  • Mimi M. Hou

    (University of Oxford
    University of Oxford)

  • Adam C. Harding

    (University of Edinburgh)

  • Natalie M. Barber

    (University of Oxford)

  • Prasun Kundu

    (University of Cambridge)

  • Florian A. Bach

    (University of Edinburgh)

  • Jo Salkeld

    (University of Oxford
    University of Oxford)

  • Yrene Themistocleous

    (University of Oxford)

  • Nicola M. Greenwood

    (University of Oxford)

  • Jee-Sun Cho

    (University of Oxford
    University of Oxford)

  • Jordan R. Barrett

    (University of Oxford
    University of Oxford)

  • Fay L. Nugent

    (University of Oxford
    University of Oxford)

  • Thomas A. Rawlinson

    (University of Oxford)

  • Susanne H. Hodgson

    (University of Oxford)

  • Baktash Khozoee

    (University of Oxford)

  • Dylan J. Lochlainn

    (University of Oxford)

  • Rachel E. Cowan

    (University of Oxford
    University of Oxford)

  • Ian D. Poulton

    (University of Oxford)

  • Megan Baker

    (University of Oxford)

  • Lucy Kingham

    (University of Oxford)

  • Celia H. Mitton

    (University of Oxford)

  • Abigail Platt

    (University of Oxford)

  • Raquel Lopez Ramon

    (University of Oxford)

  • Fernando Ramos Lopez

    (University of Oxford)

  • Merin Thomas

    (University of Oxford)

  • Katherine Skinner

    (University of Oxford
    University of Oxford)

  • Doris Quinkert

    (University of Oxford
    University of Oxford)

  • Dimitra Pipini

    (University of Oxford
    University of Oxford)

  • Amelia M. Lias

    (University of Oxford
    University of Oxford)

  • Martino Bardelli

    (University of Oxford
    University of Oxford)

  • Nick J. Edwards

    (University of Oxford)

  • Francesca R. Donnellan

    (University of Oxford
    University of Oxford)

  • Sumi Biswas

    (University of Oxford)

  • Julian C. Rayner

    (University of Cambridge)

  • Carolyn M. Nielsen

    (University of Oxford
    University of Oxford)

  • Sarah E. Silk

    (University of Oxford
    University of Oxford)

  • Simon J. Draper

    (University of Oxford
    University of Oxford
    University of Oxford)

  • Wiebke Nahrendorf

    (University of Edinburgh)

  • Philip J. Spence

    (University of Edinburgh)

  • Angela M. Minassian

    (University of Oxford
    University of Oxford
    University of Oxford)

Abstract

Clinical immunity to malaria can lead to asymptomatic infection, but the underlying mechanisms remain unclear. To examine the development of clinical immunity, we conducted a multi-cohort, repeat controlled human malaria infection (CHMI) study with Plasmodium vivax, and a heterologous rechallenge with P. falciparum (ClinicalTrials.gov NCT03797989). Malaria-naïve adults underwent CHMI up to three times, by administration of red blood cells infected with P. vivax PvW1 clone or P. falciparum 3D7 clone. Nineteen participants underwent primary CHMI with P. vivax, 12 returned for secondary homologous CHMI and 2 for tertiary homologous CHMI. Six participants who had completed P. vivax CHMI then underwent heterologous rechallenge with P. falciparum. We find that clinical immunity to P. vivax develops rapidly after a single CHMI, protecting participants against fever and laboratory abnormalities. This is underpinned by the attenuation of inflammatory cytokines and chemokines, as well as reduced coagulation and endothelium activation. In contrast, there is no evidence of anti-parasite immunity, suggesting that mechanisms of clinical immunity can operate independently of pathogen load to reduce the damage caused by malaria infection. In addition, we show that clinical immunity to P. vivax is parasite species-specific and provides no protection against CHMI with P. falciparum.

Suggested Citation

  • Mimi M. Hou & Adam C. Harding & Natalie M. Barber & Prasun Kundu & Florian A. Bach & Jo Salkeld & Yrene Themistocleous & Nicola M. Greenwood & Jee-Sun Cho & Jordan R. Barrett & Fay L. Nugent & Thomas , 2025. "Development of clinical immunity to Plasmodium vivax following repeat controlled human malaria infection," Nature Communications, Nature, vol. 16(1), pages 1-13, December.
    • Handle: RePEc:nat:natcom:v:16:y:2025:i:1:d:10.1038_s41467-025-63104-y
    DOI: 10.1038/s41467-025-63104-y
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