Development of clinical immunity to Plasmodium vivax following repeat controlled human malaria infection
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.
Article Details
Authors (39)
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. Mac 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
Angela M. Minassian