Monoclonal antibodies AC-43 and AC-29 disrupt Plasmodium vivax development in the Indian malaria vector Anopheles culicifacies (Diptera: Culicidae).
A repertoire of monoclonal antibodies (mAbs) was generated against the midgut proteins of Anopheles culicifacies mosquitoes. The mAbs AC-43 and AC-29 significantly inhibited Plasmodium vivax development inside the mosquito midgut. The number of oocysts that developed was reduced by 78.6% when mosquitoes ingested a combination of these two mAbs along with the blood meal. AC-43 mAb binds to the epitope common in 97, 80 and 43 kDa polypeptides from the midgut protein extract, as indicated by western blot analysis. Similarly, the mAb AC-29 recognized 52, 44, 40 and 29 kDa polypeptides. These female midgut-specific polypeptides are shared between An. culicifacies and An. stephensi, two major vectors of malaria in India. Deglycosylation assays revealed that O-linked carbohydrates are the major components in epitopes corresponding to AC-43 and AC-29. Gold particle labelling revealed that both these mAbs preferentially bind to glycoproteins at the apical microvilli and the microvillus-associated network present inside transverse sections of the gut epithelium. These regions are particularly known to have receptors for ookinetes, which enable them to cross this epithelial barrier and provide them with certain necessary chemicals or components for further development into oocysts. Therefore, these glycoproteins appear to be potential candidates for a vector-directed transmission-blocking vaccine (TBV).
Chugh
Manoj
M
National Institute of Pharmaceutical Education and Research, Ahmedabad 380 054, India. manoj.chugh2@gmail.com
Gulati
B R
BR
Gakhar
S K
SK
D000818:Animals; D000852:Anopheles / Q000378:metabolism* / Q000469:parasitology*; D000911:Antibodies, Monoclonal / Q000737:chemistry*; D000941:Antigens / Q000737:chemistry; D002241:Carbohydrates / Q000737:chemistry; D000939:Epitopes / Q000737:chemistry; D005260:Female; D006031:Glycosylation; D006801:Humans; D006825:Hybridomas / Q000378:metabolism; D015151:Immunoblotting / Q000379:methods; D017780:Malaria Vaccines / Q000737:chemistry; D051379:Mice; D008807:Mice, Inbred BALB C; D033661:Oocysts / Q000378:metabolism; D010966:Plasmodium vivax / Q000737:chemistry* / Q000378:metabolism
D000911:Antibodies, Monoclonal; D000941:Antigens; D002241:Carbohydrates; D000939:Epitopes; D017780:Malaria Vaccines