A vaccine targeting mosquito metabolic pathways to eradicate malaria

ABSTRACT The World Health Organization, NIH/NIAID, and other public health organizations have recently highlighted the urgent need for a mosquito pathogen transmission-blocking vaccine (TBV) to be used alongside the recent RTS,S, and R21 vaccines to eradicate malaria. Unlike traditional vaccines, TBV immunization is not of direct individual benefit. When an Anopheles mosquito feeds on a TBV-immunized human, it ingests antibodies that interrupt the development of Plasmodium gametocytes into infectious sporozoites, preventing the mosquito from transmitting the pathogen to the next person. As a result, this process disrupts the cycle of Plasmodium in mosquitoes and helps reduce its spread to humans within the community. We have developed a prototype TBV candidate that targets four novel metabolic proteins in mosquitoes. Preliminary data demonstrate a complete blockage of Plasmodium berghei transmission from mice to mosquitoes. Our long-term goal is to create a vaccine that disrupts the transmission cycle of malaria in community settings in the developing world. Our customers are global health and government organizations that call on TBVs to eradicate malaria. Surveys report that the populations currently using anti-malarial vaccines and deploying various chemical and physical interventions are very open to integrating a new TBV. This proposal aims to refine our TBV candidate by (i) removing antigens that do not contribute to transmission-blocking and (ii) extending our findings to the human pathogen Plasmodium falciparum.