Determinants of transmission-blocking properties of antibodies targeting the 6C domain of Pfs48/45 of the Plasmodium falciparum parasite

Over 400,000 people die from malaria each year; most of these resulting from infection by the Plasmodium falciparum parasite. Although the very first Malaria vaccine has been recently approved by the World Health Organization, it fails to provide long-term immunity as protection against the parasite wanes rapidly over time. This highlights the need for the development of alternative malaria vaccines that confers long-term protective immunity. One promising vaccine candidate involves immunization of individuals with a Pfs48/45 antigen (6C); a protein expressed on P. falciparum during sexual reproduction of the parasite. Immunization through this antigen induces the generation of highly potent antibodies that block transmission of the parasite to humans. However, less potent antibodies are generated as well. The generation of these low potent antibodies is problematic as it can hinder the overall immune response, confer lower levels of protection from the parasite, and result in poor efficacy of the vaccine. The production of low potency antibodies can be avoided by modifying the structure of the antigen. However, where and what types of modifications are required can only be inferred by having a molecular understanding of how these low potency antibodies interact with the antigen. The molecular insights are critical for guiding the development of a highly effective malaria vaccine; an important steppingstone in the eradication of malaria.

Basic Science

May 2022 — Apr 2023

$13,819

Canada