1. Carboxypeptidases B of Anopheles gambiae as Targets for a Plasmodium falciparum Transmission-Blocking Vaccine
- Author
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Sabine Thiberge, Catherine Lavazec, Christian Boudin, Rachida Tahar, Catherine Bourgouin, Renaud Lacroix, Sarah Bonnet, Bertrand Boisson, A. Diop, Biologie et Génétique du Paludisme, Institut Pasteur [Paris] (IP), Paludologie afrotropicale, Institut de recherche pour le développement [Dakar, Sénégal] (IRD Hann Maristes), Immunologie moléculaire des parasites, Institut Pasteur [Paris] (IP)-Centre National de la Recherche Scientifique (CNRS), and This project was supported by fellowships to C. Lavazec (F. Lacoste, CANAM, Fondation des Treilles) and research funds from the Pasteur Institute and the French Ministry of Research (PAL+ Special Program).
- Subjects
Plasmodium berghei ,Anopheles gambiae ,[SDV]Life Sciences [q-bio] ,Immunology ,Plasmodium falciparum ,Biology ,Microbiology ,Plasmodium ,Antibodies ,Mice ,parasitic diseases ,Anopheles ,Malaria Vaccines ,medicine ,Parasite hosting ,Animals ,Humans ,Malaria, Falciparum ,Reproduction ,fungi ,Midgut ,biology.organism_classification ,medicine.disease ,Virology ,Carboxypeptidase ,Carboxypeptidase B ,Malaria ,Up-Regulation ,Gastrointestinal Tract ,Disease Models, Animal ,Infectious Diseases ,Microbial Immunity and Vaccines ,biology.protein ,Parasitology ,Female - Abstract
Anopheles gambiae is the major African vector of Plasmodium falciparum , the most deadly species of human malaria parasite and the most prevalent in Africa. Several strategies are being developed to limit the global impact of malaria via reducing transmission rates, among which are transmission-blocking vaccines (TBVs), which induce in the vertebrate host the production of antibodies that inhibit parasite development in the mosquito midgut. So far, the most promising components of a TBV are parasite-derived antigens, although targeting critical mosquito components might also successfully block development of the parasite in its vector. We previously identified A. gambiae genes whose expression was modified in P. falciparum -infected mosquitoes, including one midgut carboxypeptidase gene, cpbAg1. Here we show that P. falciparum up-regulates the expression of cpbAg1 and of a second midgut carboxypeptidase gene, cpbAg2 , and that this up-regulation correlates with an increased carboxypeptidase B (CPB) activity at a time when parasites establish infection in the mosquito midgut. The addition of antibodies directed against CPBAg1 to a P. falciparum -containing blood meal inhibited CPB activity and blocked parasite development in the mosquito midgut. Furthermore, the development of the rodent parasite Plasmodium berghei was significantly reduced in mosquitoes fed on infected mice that had been immunized with recombinant CPBAg1. Lastly, mosquitoes fed on anti-CPBAg1 antibodies exhibited reduced reproductive capacity, a secondary effect of a CPB-based TBV that could likely contribute to reducing Plasmodium transmission. These results indicate that A. gambiae CPBs could constitute targets for a TBV that is based upon mosquito molecules.
- Published
- 2007