Expression, Immunogenicity, Histopathology, and Potency of a Mosquito-Based Malaria Transmission-Blocking Recombinant Vaccine

ABSTRACTVaccines have been at the forefront of global research efforts to combat malaria, yet despite several vaccine candidates, this goal has yet to be realized. A potentially effective approach to disrupting the spread of malaria is the use of transmission-blocking vaccines (TBV), which prevent the development of malarial parasites within their mosquito vector, thereby abrogating the cascade of secondary infections in humans. Since malaria is transmitted to human hosts by the bite of an obligate insect vector, mosquito species in the genusAnopheles, targeting mosquito midgut antigens that serve as ligands forPlasmodiumparasites represents a promising approach to breaking the transmission cycle. The midgut-specific anopheline alanyl aminopeptidase N (AnAPN1) is highly conserved acrossAnophelesvectors and is a putative ligand forPlasmodiumookinete invasion. We have developed a scalable, high-yieldEscherichia coliexpression and purification platform for the recombinant AnAPN1 TBV antigen and report on its marked vaccine potency and immunogenicity, its capacity for eliciting transmission-blocking antibodies, and its apparent lack of immunization-associated histopathologies in a small-animal model.