Antibodies elicited by a chimeric peritrophin antigen reduce Aedes aegypti survival after blood feeding

Vector-borne diseases transmitted by Aedes aegypti, including dengue, Zika, chikungunya, and yellow fever, represent a persistent and expanding global health threat. Limitations of conventional vector control strategies, such as insecticide use and environmental source reduction, particularly in urban settings, underscore the need for novel and complementary tools. Anti-vector vaccination offers one such strategy by inducing host-derived antibodies that are ingested during vector feeding and interfere with vector physiology or survival. Although this concept has been successfully explored in some hematophagous arthropods, it remains largely unexplored in mosquitoes. Here, we investigated mosquito peritrophins, structural components of the midgut peritrophic matrix, as potential targets for vector-directed vaccination. We designed and recombinantly expressed a chimeric antigen, PT-3, incorporating immunogenic regions from three Aedes aegypti peritrophins/peritrophin-like proteins: AAEL002495, AAEL002467, and AAEL004798. The ability of PT-3 to elicit functional antibodies was evaluated in a bovine host model. Immunization induced a robust antigen-specific humoral response, and mosquitoes fed blood supplemented with immune sera from vaccinated animals showed significantly reduced post-feeding survival compared with controls. Consistent with this functional effect, anti-PT-3 immune sera recognized native mosquito midgut components in ELISA and Western blot assays. Overall, results are consistent with antibody-mediated interference with midgut physiological processes during blood digestion, while no significant effects on oviposition or egg viability were observed among surviving females. Together, these findings provide proof-of-concept that mosquito peritrophins can serve as immunological targets for anti-vector vaccination and provide a rationale for further developing peritrophin-targeted strategies, including alternative delivery platforms, as complementary tools for arboviral control.