The AnAPN1 mosquito-based malaria transmission-blocking vaccine
The Anopheline mosquito midgut-specific alanyl aminopeptidase N (AnAPN1) is a highly conserved luminal midgut surface glycoprotein that is involved in bloodmeal digestion. We have recently shown that antibodies elicited against this antigen can significantly block parasite development in the mosquito and the subsequent cascade of secondary infections once the mosquito takes a bloodmeal from another individual. This type of transmission-blocking vaccine (TBV) is termed "mosquito-based", since it differs from other malaria TBVs which are targeting parasite surface antigens.
The profile for the AnAPN1 TBV is as follows:
- The target is a mosquito midgut molecule which mediates ookinete invasion
- The midgut molecule is conserved across all major anopheline vectors in malaria endemic regions
- No selection pressure (i.e., mosquitoes do not die from the antibodies against AnAPN1)
- AnAPN1 appears to be important for P. falciparum and P. vivax transmission through the mosquito
- Highly immunogenic with or without adjuvant
- Safe in animal models (rodents and non-human primates)
- TBV delivery system that allows for repeated boosting after a single inoculation
Given the characteristics of this vaccine, we hypothesize that we can potentially block all 5 malaria parasite species that infect man since AnAPN1 is highly conserved across all of the anopheline species tested thus far.
[Stay tuned for the upcoming publications regarding those bullet points above without hyperlinks].
This project is supported by the PATH-Malaria Vaccine Initiative.