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Infection and Immunity, April 2007, p. 1635-1642, Vol. 75, No. 4
0019-9567/07/$08.00+0 doi:10.1128/IAI.00864-06
Copyright © 2007, American Society for Microbiology. All Rights Reserved.
Carboxypeptidases B of Anopheles gambiae as Targets for a Plasmodium falciparum Transmission-Blocking Vaccine
C. Lavazec,1,
C. Boudin,2
R. Lacroix,1
S. Bonnet,3,
A. Diop,2
S. Thiberge,1
B. Boisson,1
R. Tahar,1,
and
C. Bourgouin1*
Unité de Biologie et Génétique du Paludisme, Institut Pasteur, 25 rue du Dr Roux, 75015 Paris, France,1 Paludologie Afrotropicale, Unité 77, IRD, Dakar, Sénégal,2 Unite d'Immunologie Moléculaire des Parasites, Institut Pasteur, 25 rue du Dr Roux, 75015 Paris, France3
Received 31 May 2006/ Returned for modification 16 July 2006/ Accepted 24 January 2007
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.
* Corresponding author. Mailing address: Unité de Biologie et Génétique du Paludisme, Institut Pasteur, 25 rue du Dr Roux, 75015 Paris, France. Phone: 33-1-45-68-82-24. Fax: 33-1-40-61-30-89. E-mail: cabourg{at}pasteur.fr.
Published ahead of print on 5 February 2007.
Present address: Unité d'Immunologie Moléculaire des Parasites, Institut Pasteur, 28 rue du Dr Roux, 75015 Paris, France.
Present address: Ecole Nationale Vétérinaire, UMR ENVN/INRA 1034, Atlanpole-La Chantrerie, B.P. 40706, 44307 Nantes cedex 03, France.
Present address: Laboratoire de Recherche sur le Paludisme, OCEAC BP 288, Yaoundé, Cameroon.
Infection and Immunity, April 2007, p. 1635-1642, Vol. 75, No. 4
0019-9567/07/$08.00+0 doi:10.1128/IAI.00864-06
Copyright © 2007, American Society for Microbiology. All Rights Reserved.
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