Virus-like particle-based vaccines targeting theAnophelesmosquito salivary protein, TRIO

Abstract

ABSTRACTMalaria is a highly lethal infectious disease caused byPlasmodiumparasites. These parasites are transmitted to vertebrate hosts when mosquitoes of theAnophelesgenus probe for a blood meal. Sporozoites, the infectious stage ofPlasmodium, 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 againstPlasmodium, we produced a virus-like particle (VLP)-based vaccine displaying an epitope of TRIO, anAnophelessalivary protein which 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 aPlasmodiumtargeted 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 thePlasmodium falciparumcircumsporozoite 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.