Summary: Inhibiting transmission of Plasmodium is a central strategy in malarial eradication, and the biological process of gamete fusion during fertilization is a proven target for this approach.The lack of a structure or known molecular function of current anti-malarial vaccine targets has previously been a hindrance in the development of transmission-blocking vaccines.Structure/function studies have indicated that the conserved gamete membrane fusion protein HAP2 is a class II viral fusion protein.
Here, we demonstrate that targeting a function-critical site of the fusion/cd loop with species-specific Foam Tape antibodies reduces Plasmodium berghei transmission in vivo by 58.9% and in vitro fertilization by up to 89.9%.
A corresponding reduction in P.falciparum transmission (75.5%/36.
4% reductions in intensity/prevalence) is observed in complimentary field studies.These results emphasize conserved mechanisms of fusion in Apicomplexa, while highlighting an approach to design future anti-malarial transmission-blocking vaccines.: Angrisano et al.
find that the HAP2 cd-loop can be targeted as an anti-malarial intervention, is immunogenic CHROMIUM PLUS across multiple plasmodial species, can induce antibodies that specifically recognize the sexual stages of the parasitic life cycle, and can mediate transmission-blocking immunity in the lab and the field.Keywords: HAP2, malaria, transmission, fusion, vaccine.