h Malaria transmission-blocking vaccines (TBVs) represent a promising approach for the elimination and eradication of this disease. AnAPN1 is a lead TBV candidate that targets a surface antigen on the midgut of the obligate vector of the Plasmodium parasite, the Anopheles mosquito. In this study, we demonstrated that antibodies targeting AnAPN1 block transmission of Plasmodium falciparum and Plasmodium vivax across distantly related anopheline species in countries to which malaria is endemic. Using a biochemical and immunological approach, we determined that the mechanism of action for this phenomenon stems from antibody recognition of a single protective epitope on AnAPN1, which we found to be immunogenic in murine and nonhuman primate models and highly conserved among anophelines. These data indicate that AnAPN1 meets the established target product profile for TBVs and suggest a potential key role for an AnAPN1-based panmalaria TBV in the effort to eradicate malaria.

Malaria sporozoites are deposited into the skin by mosquitoes and infect hepatocytes. The molecular basis of how Plasmodium falciparum sporozoites migrate through host cells is poorly understood, and direct evidence of its importance in vivo is lacking. Here, we generated traversal-deficient sporozoites by genetic disruption of sporozoite microneme protein essential for cell traversal (PfSPECT) or perforin-like protein 1 (PfPLP1). Loss of either gene did not affect P. falciparum growth in erythrocytes, in contrast with a previous report that PfPLP1 is essential for merozoite egress. However, although traversal-deficient sporozoites could invade hepatocytes in vitro, they could not establish normal liver infection in humanized mice. This is in contrast with NF54 sporozoites, which infected the humanized mice and developed into exoerythrocytic forms. This study demonstrates that SPECT and perforin-like protein 1 (PLP1) are critical for transcellular migration by P. falciparum sporozoites and demonstrates the importance of cell traversal for liver infection by this human pathogen.

Aedes albopictus is a potential West Nile virus bridge vector in Northern Virginia; however, information regarding its virus transmission dynamics is limited, as this species is not readily collected in existing traps. This study used 5 replicates of a 5 x 5 Latin square to evaluate the efficiency and effectiveness of 2 novel host-seeking mosquito traps (the BG-Sentinel and the Collapsible Mosquito Trap (CMT-20) in collecting Ae. albopictus, relative to a carbon dioxide (CO2)-baited Centers for Disease Control and Prevention (CDC) miniature light trap. When used with CO2, the BG-Sentinel (with BG-Lure) collected 33 times more female Ae. albopictus per 24-h trapping period than did the CO2-baited CDC light trap. Without CO2, the BG-Sentinel (with BG-Lure) still collected over 6 times as many female Ae. albopictus as the CO2-baited CDC trap. Both configurations of the BG-Sentinel were significantly more effective than the other traps. The BG-Sentinel was also significantly more efficient in collecting Ae. albopictus and collected a high proportion of this species, both with CO2 and without CO2. The CMT-20 (with SkinLure) collected significantly more Ae. albopictus when used with CO2 than without CO2, but did not collect significantly more Ae. albopictus than the CO2-baited CDC light trap. The proportion of Ae. albopictus collected in the CMT-20 with CO2 and without CO2 did not differ significantly from the proportion of Ae. albopictus collected in the CDC trap.

fVaccines 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 transmissionblocking 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 genus Anopheles, targeting mosquito midgut antigens that serve as ligands for Plasmodium parasites represents a promising approach to breaking the transmission cycle. The midgut-specific anopheline alanyl aminopeptidase N (AnAPN1) is highly conserved across Anopheles vectors and is a putative ligand for Plasmodium ookinete invasion. We have developed a scalable, high-yield Escherichia coli expression 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.