Last Updated: 03/12/2025
Using the Controlled Human Malaria Infection Model to Assess Functional Laboratory Assays of Immunity to Malaria
Objectives
This project proposes to use a controlled human malaria infection (CHMI) model administered to volunteers with varying degrees of prior exposure to malaria (and therefore natural immunity), to examine the relationship between the growth inhibitory activity assay (GIA) and the antibody-dependent respiratory burst (ADRB) assay readouts and parasite multiplication rates (PMR). It will also seek to describe immunological signatures associated with protection by performing gene expression analyses on these volunteers post-CHMI.
A validated assay that correlates with natural immunity to malaria and could predict blood-stage vaccine efficacy would have huge application, reducing the cost and ethical risks associated with efficacy testing and helping prioritise progression of only the most promising vaccines to field studies. Two functional assays have been proposed as key potential correlates of protective immunity: the growth inhibitory activity assay (GIA) and the antibody-dependent respiratory burst (ADRB) assay. However, neither has been validated as a surrogate of protective immunity due to the absence of a protective vaccine candidate. An elegant and novel approach to validate these assays is to use the controlled human malaria infection (CHMI) model. CHMI studies have become a routine tool to evaluate the efficacy of anti-malarial drugs and vaccines, but have never been conducted in volunteers with prior exposure to malaria.
Aug 2012 — Jul 2016
$302,048


