A vaccine targeting mosquito metabolic pathways to eradicate malaria

The National Institute of Allergy and Infectious Diseases awarded $599,709 to L2 Diagnostics LLC on September 23, 2025, under the Allergy and Infectious Diseases Research program (CFDA 93.855) to develop a transmission-blocking vaccine targeting mosquito metabolic pathways to interrupt malaria spread.

L2 Diagnostics LLC, a for-profit small business based in Woodbridge, Connecticut, is refining a prototype vaccine candidate that targets four novel metabolic proteins in Anopheles mosquitoes. The vaccine works by inducing antibodies in immunized humans that block the development of Plasmodium gametocytes into infectious sporozoites when ingested by mosquitoes, preventing onward transmission to other humans. Preliminary data demonstrate complete blockage of Plasmodium berghei transmission from mice to mosquitoes. The project will remove antigens that do not contribute to transmission-blocking activity and extend findings to Plasmodium falciparum, the human malaria pathogen.

Work is performed in New Haven, Connecticut. The period of performance runs through August 31, 2027. The award is structured as a Project Grant, an assistance type supporting research institutions and individuals in biomedical research within infectious diseases.

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.