Virus-like particle-based vaccines targeting the Anopheles mosquito salivary protein TRIO.

Abstract

Malaria is a highly lethal infectious disease caused by Plasmodium parasites. These parasites are transmitted to vertebrate hosts when mosquitoes of the Anopheles genus probe for a blood meal. Sporozoites, the infectious stage of Plasmodium, transit to the liver within hours of injection into the dermis. Vaccine efforts are hindered by the complexity of the parasite's lifecycle and the speed at which the infection is established in the liver. In an effort to enhance immunity against Plasmodium, we produced a virus-like particle (VLP)-based vaccine displaying an epitope of TRIO, an Anopheles salivary protein that has been shown to enhance mobility and dispersal of sporozoites in the dermis. Previous work demonstrated that passive immunization with TRIO offered protection from liver infection and acted synergistically with a Plasmodium-targeted vaccine. Immunization of mice with TRIO VLPs resulted in high-titer and long-lasting antibody responses that did not significantly drop for over 18 months post-immunization. TRIO VLPs were similarly immunogenic when combined with an anti-malaria vaccine targeting the L9 epitope of the Plasmodium falciparum circumsporozoite protein. However, when used in a malaria challenge mouse model, TRIO VLPs only provided modest protection from infection and did not boost the protection provided by L9 VLPs.IMPORTANCEProteins present in the salivary glands of mosquitos have been shown to enhance the transmission efficiency of mosquito-borne pathogens, suggesting that interventions targeting the activity of these proteins could reduce transmission. Here, we looked at the efficacy of a vaccine targeting TRIO, an Anopheles mosquito salivary protein that has been reported to enhance Plasmodium falciparum malaria infection. We show that this vaccine can elicit strong anti-TRIO antibody responses, but these antibodies only result in a modest decrease in infection.