Immunization with mosquito AgTRIO protein to prevent malaria

PROJECT SUMMARYMalaria is one of the world’s major public health threats. The disease is transmitted
when an infected female Anopheles mosquito, while probing for a blood meal, injects saliva
together with Plasmodium sporozoites into the skin of the vertebrate host (1, 2). To date, a
highly effective, safe and FDA-approved human vaccine against malaria has not been
developed. The most established malaria vaccine candidate, RTS,S/AS01, which is a
recombinant protein based on the circumsporozoite protein of Plasmodium falciparum, confers
moderate protection against malaria which wanes over time (1-10). There is great need for an
improved vaccine against malaria, and that is the goal of this proposal - using a protein in
mosquito saliva that influences the ability of Plasmodium sporozoites to infect the vertebrate
host.In our recently published study (11), we identified a protein in the saliva of female
Anopheles gambiae mosquitoes, named AgTRIO. We produced recombinant AgTRIO in
Escherichia coli and demonstrated that active immunization of mice with recombinant AgTRIO
significantly reduced mosquito-borne Plasmodium berghei and Plasmodium falciparum infection
of the animals. This work showed that a protein in mosquito saliva can be targeted to prevent
Plasmodium infection.The aim of this proposal is to develop a strategy for active immunization with AgTRIO
protein produced in a eukaryotic expression system. Our long-term goal is to develop a vaccine
that will provide robust protection against malaria for use in humans.PROJECT NARRATIVEThe devastating effects of malaria underscore the urgent need for effective control
measures against the disease. The proposed project is relevant to public health because it will
propel the discovery of new targets for malaria vaccine development, which is critical for the
achievement of malaria eradication.