GIUSEPPE BALISTRERI

LEA KLINGENBERG BARFOD
Centre for translational Medicine and Parasitology (CMP)
University of Copenhagen 

Targeting complement immune evasion mechanism in P. falciparum for the development of next generation malaria vaccines

Area of expertise: Malaria immunology, monoclonal antibody discovery, epitope characterisation, immune evasion mechanisms, and vaccine development

Abstract: Plasmodium falciparum is responsible for the majority of malaria infections and deaths worldwide. Natural immunity to blood stage infection is acquired over several exposures to the parasite and is thought to rely on antibodies. Antibodies can protect from severe disease through different effector functions, with complement activation lately emerging as an important feature of protective humoral responses to malaria infection. Malaria parasites have, however, evolved several mechanisms to evade complement attack, including the recruitment of complement down-regulatory proteins like Factor H (FH) and C1 esterase inhibitor (C1-INH) to the merozoite. Current vaccine development strategies include targeting merozoite antigens, we therefore wanted to investigate the impact of the complement evasion mechanism and the possibilities that it can be counteracted by antibodies or other reagents.

In this talk, I will present data on the role of naturally acquired antibodies towards the malaria antigens involved in the evasion mechanism, as well as our discovery of a third complement regulatory protein recruited to the merozoite surface. Further the development of de novo designed minibinders binding both the recruiting antigens as well as the current blood stage vaccine candidate RH5 will be presented.