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Infection and Immunity, April 2003, p. 2032-2040, Vol. 71, No. 4
0019-9567/03/$08.00+0     DOI: 10.1128/IAI.71.4.2032-2040.2003
Copyright © 2003, American Society for Microbiology. All Rights Reserved.

Induction of Mosquitocidal Activity in Mice Immunized with Anopheles gambiae Midgut cDNA

B. D. Foy,^1* T. Magalhaes,¹ W. E. Injera,¹ I. Sutherland,¹ M. Devenport,² A. Thanawastien,³ D. Ripley,³ L. Cárdenas-Freytag,³ and J. C. Beier¹

Department of Tropical Medicine,¹ Department of Microbiology and Immunology, Tulane University, New Orleans, Louisiana,³ Department of Genetics, Case Western Reserve University, Cleveland, Ohio²

Received 23 October 2002/ Returned for modification 24 December 2002/ Accepted 7 January 2003

Vaccines that induce mosquito-killing (mosquitocidal) activity could substantially reduce the transmission of certain mosquito-borne diseases, especially vaccines against African malaria vectors, such as the mosquito Anopheles gambiae. To generate and characterize antimosquito immunity we immunized groups of mice with two individual A. gambiae midgut cDNAs, Ag-Aper1 (a secreted peritrophic matrix protein) and AgMuc1 (a midgut-bound mucin), and an A. gambiae midgut cDNA library from blood-fed mosquitoes. We observed significantly increased mortality among mosquitoes that fed on either the AgMuc1- or the cDNA library-immunized mice compared to that of controls, but no differences were observed among those fed on Ag-Aper1-immunized mice. Analysis of the humoral and cellular immune responses from mice showed that the induced mosquitocidal effect was associated with immune profiles characterized by elevated tumor necrosis factor alpha and gamma interferon cytokine levels and very low antibody titers. Furthermore, an additional immunization of cDNA library-immunized mice with midgut protein shifted immunity toward a Th2-type immune response, characterized by elevated antibody titers and high interleukin-5 and interleukin-10 cytokine levels; importantly, mosquitoes feeding on these mice exhibited no undo mortality. Finally, when immune sera was ingested by mosquitoes through a membrane feeder, no effect on mosquito mortality was observed, indicating that serum factors alone were not responsible for the mosquitocidal effect. Our results demonstrate that mosquitocidal immunity in mice can be consistently generated by midgut cDNA immunization and suggest this cDNA-induced mosquitocidal immunity is cell mediated.

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* Corresponding author. Present address: Colorado State University, Arthropod-Borne and Infectious Diseases Laboratory (AIDL), Fort Collins, CO. Phone: (970) 491-4383. Fax: (970) 491-8323. E-mail: brian.foy{at}colostate.edu.

Editor: W. A. Petri, Jr.

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Infection and Immunity, April 2003, p. 2032-2040, Vol. 71, No. 4
0019-9567/03/$08.00+0     DOI: 10.1128/IAI.71.4.2032-2040.2003
Copyright © 2003, American Society for Microbiology. All Rights Reserved.

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