Alanyl aminopeptidase N (AnAPN1) (AnAPN1)

Alanyl aminopeptidase N (AnAPN1) is a zinc-dependent metalloprotease anchored to the luminal surface of the midgut epithelium in Anopheles mosquitoes (UniProt Q7Q2T8). It plays a dual role in the mosquito's physiology, participating in the digestion of bloodmeals by cleaving N-terminal amino acids from peptides and serving as a critical receptor for Plasmodium ookinetes during their invasion of the midgut epithelium (Atkinson et al., 2015). Because it is essential for the parasite's development within the vector, AnAPN1 has become a primary target for transmission-blocking vaccines (TBVs) (Bender et al., 2021). In this strategy, humans are immunized with recombinant AnAPN1 to produce specific antibodies; when a mosquito bites an immunized person, it ingests these antibodies, which then bind to AnAPN1 in the mosquito's gut and prevent the parasite from establishing an infection (Dinglasan et al., 2007). This "mosquito-based" approach is unique because it targets a conserved vector protein rather than a highly polymorphic parasite antigen, potentially offering broad protection against multiple Plasmodium species (Atkinson et al., 2015; NCT05905432).

Other names

AgAPN1AsAPN1Aminopeptidase N1APN1Anopheles gambiae alanyl aminopeptidase NAnopheles stephensi alanyl aminopeptidase NCD13-like proteinAgaP_AGAP004809

Transmission-blocking antibodies (induced by vaccination or administered as monoclonal antibodies) bind to AnAPN1 on the mosquito midgut luminal surface, sterically hindering Plasmodium ookinete attachment and invasion of the midgut epithelium, thereby preventing the parasite from completing its life cycle in the vector (Atkinson et al., 2015; Dinglasan et al., 2007).