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

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 A. Rawlinson, Susanne H. Hodgson, Baktash Khozoee, Dylan J. Lochlainn, Rachel E. Cowan, Ian D. Poulton, Megan Baker, Lucy Kingham, Celia H. Mitton, Abigail Platt, Raquel Lopez Ramon, Fernando Ramos Lopez, Merin Thomas, Katherine Skinner, Doris Quinkert, Dimitra Pipini, Amelia M. Lias, Martino Bardelli, Nick J. Edwards, Francesca R. Donnellan, Sumi Biswas, Julian C. Rayner, Carolyn M. Nielsen, Sarah E. Silk, Simon J. Draper, Wiebke Nahrendorf, Philip J. Spence () and Angela M. Minassian ()
Additional contact information
Mimi M. Hou: 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
Yrene Themistocleous: University of Oxford
Nicola M. Greenwood: University of Oxford
Jee-Sun Cho: University of Oxford
Jordan R. Barrett: University of Oxford
Fay L. Nugent: 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
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
Doris Quinkert: University of Oxford
Dimitra Pipini: University of Oxford
Amelia M. Lias: University of Oxford
Martino Bardelli: University of Oxford
Nick J. Edwards: University of Oxford
Francesca R. Donnellan: University of Oxford
Sumi Biswas: University of Oxford
Julian C. Rayner: University of Cambridge
Carolyn M. Nielsen: University of Oxford
Sarah E. Silk: University of Oxford
Simon J. Draper: University of Oxford
Wiebke Nahrendorf: University of Edinburgh
Philip J. Spence: University of Edinburgh
Angela M. Minassian: University of Oxford

Nature Communications, 2025, vol. 16, issue 1, 1-13

Abstract: 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.

Date: 2025
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DOI: 10.1038/s41467-025-63104-y

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