Development of clinical immunity to Plasmodium vivax following repeat controlled human malaria infection
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.
Authors
- Lucy Kingham-Page (ORCID: https://orcid.org/0000-0001-7891-6359)
- Adam Harding (ORCID: https://orcid.org/0000-0003-1479-959X)
- Abigail Platt
- Francesca R. Donnellan (ORCID: https://orcid.org/0000-0002-4723-3560)
- Baktash Khozoee (ORCID: https://orcid.org/0000-0002-2470-3283)
- Natalie M. Barber
- Carolyn M. Nielsen (ORCID: https://orcid.org/0000-0002-9033-1318)
- Dylan J. Mac Lochlainn (ORCID: https://orcid.org/0000-0001-9181-8112)
- Thomas A. Rawlinson
- Katherine Skinner
- Dimitra Pipini (ORCID: https://orcid.org/0000-0002-2230-6364)
- Fernando Ramos Lopez (ORCID: https://orcid.org/0000-0002-9997-7879)
- Jordan R. Barrett (ORCID: https://orcid.org/0000-0003-0746-1945)
- Martino Bardelli (ORCID: https://orcid.org/0000-0002-1611-7655)
- Jee-Sun Cho
- Ian Poulton (ORCID: https://orcid.org/0000-0002-6603-8461)
- Doris Quinkert (ORCID: https://orcid.org/0000-0003-4135-6452)
- Rachel E. Cowan (ORCID: https://orcid.org/0000-0002-3320-0653)
- Philip J. Spence (ORCID: https://orcid.org/0000-0002-5506-2773)
- Florian A. Bach (ORCID: https://orcid.org/0000-0002-0126-5516)
- Wiebke Nahrendorf (ORCID: https://orcid.org/0000-0002-4503-8761)
- Simon J. Draper (ORCID: https://orcid.org/0000-0002-9415-1357)
- Fay L. Nugent (ORCID: https://orcid.org/0000-0001-6312-7293)
- Sumi Biswas (ORCID: https://orcid.org/0000-0001-8507-7282)
- Angela M. Minassian (ORCID: https://orcid.org/0000-0001-7832-9824)
- Mimi M. Hou (ORCID: https://orcid.org/0000-0002-8517-9147)
- Julian C. Rayner (ORCID: https://orcid.org/0000-0002-9835-1014)
- Celia Mitton
- Sarah E. Silk (ORCID: https://orcid.org/0000-0003-0563-4814)
- Nicola M. Greenwood
- Susanne H. Hodgson (ORCID: https://orcid.org/0000-0002-0895-3442)
- Merin Thomas (ORCID: https://orcid.org/0000-0003-3482-7199)
- Nick J. Edwards (ORCID: https://orcid.org/0000-0002-7030-7839)
- Raquel Lopez Ramon
- Amelia M. Lias (ORCID: https://orcid.org/0000-0003-2939-7761)
- Prasun Kundu (ORCID: https://orcid.org/0000-0001-6481-3412)
- Jo Salkeld (ORCID: https://orcid.org/0000-0002-7868-7071)
- Yrene Themistocleous (ORCID: https://orcid.org/0000-0001-9285-6639)
- Megan Baker
Institutions
- University of Cambridge (GB)
- University of Oxford (GB)
- Oxford BioMedica (United Kingdom) (GB)
- Jenner Institute (GB)
- University of Edinburgh (GB)
Publication Details
- Journal
- Nature Communications
- Published
- 2025-09-25
- DOI
- https://doi.org/10.1038/s41467-025-63104-y
- Citations
- 2
- Primary Topic
- Malaria Research and Control
- Type
- article
- Field-Weighted Citation Impact
- 3.76
Funders
- Wellcome Trust
- National Institute for Health and Care Research
- Department of Health and Social Care
- University of Oxford
- European Commission
- Oxford University Hospitals NHS Foundation Trust
- Medical Research Council