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Am. J. Trop. Med. Hyg., 76(6), 2007, pp. 1072-1078
Copyright © 2007 by The American Society of Tropical Medicine and Hygiene

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GENETIC CONTROL OF MALARIA PARASITE TRANSMISSION: THRESHOLD LEVELS FOR INFECTION IN AN AVIAN MODEL SYSTEM

NIJOLE JASINSKIENE, JUDY COLEMAN, AURORA ASHIKYAN, MICHAEL SALAMPESSY, OSVALDO MARINOTTI, AND ANTHONY A. JAMES*
Department of Molecular Biology and Biochemistry, University of California, Irvine, California; Department of Microbiology and Molecular Genetics, University of California, California

Genetic strategies for controlling malaria transmission based on engineering pathogen resistance in Anopheles mosquitoes are being tested in a number of animal models. A key component is the effector molecule and the efficiency with which it reduces parasite transmission. Single-chain antibodies (scFvs) that bind the circumsporozoite protein of the avian parasite, Plasmodium gallinaceum, can reduce mean intensities of sporozoite infection of salivary glands by two to four orders of magnitude in transgenic Aedes aegypti. Significantly, mosquitoes with as few as 20 sporozoites in their salivary glands are infectious for a vertebrate host, Gallus gallus. Although scFvs hold promise as effector molecules, they will have to reduce mean intensities of infection to zero to prevent parasite transmission and disease. We conclude that similar endpoints must be reached with human pathogens if we are to expect an effect on disease transmission.

Received December 12, 2006. Accepted for publication January 31, 2007.

Acknowledgments: The authors thank the members of our laboratory for discussions and Lynn M. Olson for help in preparing the manuscript.

Financial support: This work was supported by awards from the National Institutes of Health (AI29746 and AI44800) and the Burroughs-Wellcome Fund.

* Address correspondence to Anthony A. James, Department of Microbiology and Molecular Genetics, Department of Molecular Biology and Biochemistry, 3205 McGaugh Hall, University of California, Irvine CA 92697-3900. E-mail: aajames{at}uci.edu

Authors’ addresses: Nijole Jasinskiene, Judy Coleman, Aurora Ashikyan, Michael Salampessy, Osvaldo Marinotti, and Anthony A. James, 3205 McGaugh Hall, MB&B, University of California, Irvine, CA 92697-3900. E-mail: aajames{at}uci.edu.




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Comparative genomics allows the discovery of cis-regulatory elements in mosquitoes
PNAS, March 3, 2009; 106(9): 3053 - 3058.
[Abstract] [Full Text] [PDF]


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