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Last Updated: 19/07/2023

The mechanisms and dynamics of malaria transmission blocking immunity

Objectives

 

This study aims to:

  1. Identify effectors of Plasmodium transmission modulation;
  2. Characterise the dynamics of sexual-stage immune responses; and
  3. Examine the maintenance and effectiveness of transmission modulating immunity.
Principal Investigators / Focal Persons

William Stone

Rationale and Abstract

Some individuals who are naturally exposed to malaria infection acquire immune responses that stop Plasmodium development in the mosquito gut, whilst others are highly infectious despite relatively low gametocyte densities. The researcher intend to investigate naturally acquired malaria transmission modulating immunity to improve our understanding of malaria transmission and provide insight for malaria vaccinologists. 

Immune profiling by Protein micro-array and luminex (cross-sectional samples with transmission endpoints) will be used to identify effectors of Plasmodium transmission modulation that will result in a comprehensive list of antibody correlates of transmission-blocking immunity (TBI), a serological platform for assessing sexual-stage antibody titres, and a statistical model determining the impact of antibody, parasite and cytokine metrics on the association between gametocyte density and mosquito infection.

Luminex (longitudinal cohort samples) will be used to characterise the dynamics of sexual-stage immune responses that would estimate the association between gametocyte density and antibody titre and improve understanding of the dynamics of immune response to gametocytes after natural and controlled malaria exposure.

Lab-based mosquito feeding assays, B-cell assays will be used to examine the maintenance and effectiveness of transmission modulating immunity and will generate novel assays for the quantification of sexual-stage immune memory and detailed analyses of the relationship between antibody titre and transmission modulation (transmission enhancement and reduction).
 

Date

Aug 2020 — Jul 2024

Total Project Funding

$373,488

Funding Details
Wellcome Trust, United Kingdom

218676/Z/19/Z
GBP300,000
Sir Henry Wellcome Postdoctoral Fellowship
Project Site

United Kingdom

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