Targeting the mosquito prefoldin-chaperonin complex blocks Plasmodium transmission.

Area of Science:

• * Vector biology
• * Parasitology
• * Immunology

Background:

• * Malaria parasite transmission relies on host factors within the mosquito midgut.
• * The mosquito prefoldin (PFDN)-chaperonin system is crucial for protein folding and macromolecular complex assembly.
• * This system represents a potential target for novel transmission-blocking therapeutics.

Purpose of the Study:

• * To investigate the Anopheles mosquito prefoldin (PFDN)-chaperonin system as a transmission-blocking target for Plasmodium parasites.
• * To evaluate the impact of inhibiting PFDN or its CCT/TRiC partner on Plasmodium infection loads.
• * To assess the potential of this system for developing multi-species transmission-blocking vaccines.

Main Methods:

• * RNA interference (RNAi) was used to silence prefoldin subunits or the CCT/TRiC partner in mosquitoes.
• * Co-feeding assays involved administering PFDN6-specific antibodies with Plasmodium gametocytes to mosquitoes.
• * Assays were conducted in mice using malaria transmission-blocking vaccines and antibody co-feeding methods.

Main Results:

• * Silencing any prefoldin subunit or the CCT/TRiC partner significantly reduced Plasmodium falciparum oocyst loads in the mosquito midgut.
• * Co-feeding mosquitoes with PFDN6-specific antibodies also reduced parasite loads.
• * Inhibition of the PFDN-CCT/TRiC complex disrupted midgut epithelial and extracellular matrix integrity, triggering immune responses and impairing parasite immune evasion.

Conclusions:

• * The conserved Anopheles mosquito prefoldin (PFDN)-chaperonin system is a potent, multi-species transmission-blocking target.
• * Targeting this system offers a promising strategy for controlling malaria transmission.
• * Further research is warranted to explore its full potential as a vaccine target.