Virus-expressed, recombinant single-chain antibody blocks sporozoite infection of salivary glands in Plasmodium gallinaceum-infected Aedes aegypti.

M de Lara Capurro Department of Molecular Biology and Biochemistry, University of California, Irvine 92697-3900, USA.

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J Coleman Department of Molecular Biology and Biochemistry, University of California, Irvine 92697-3900, USA.

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B T Beerntsen Department of Molecular Biology and Biochemistry, University of California, Irvine 92697-3900, USA.

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K M Myles Department of Molecular Biology and Biochemistry, University of California, Irvine 92697-3900, USA.

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K E Olson Department of Molecular Biology and Biochemistry, University of California, Irvine 92697-3900, USA.

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E Rocha Department of Molecular Biology and Biochemistry, University of California, Irvine 92697-3900, USA.

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A U Krettli Department of Molecular Biology and Biochemistry, University of California, Irvine 92697-3900, USA.

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A A James Department of Molecular Biology and Biochemistry, University of California, Irvine 92697-3900, USA.

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Transgenic mosquitoes resistant to malaria parasites are being developed to test the hypothesis that they may be used to control disease transmission. We have developed an effector portion of an antiparasite gene that can be used to test malaria resistance in transgenic mosquitoes. Mouse monoclonal antibodies that recognize the circumsporozoite protein of Plasmodium gallinaceum can block sporozoite invasion of Aedes aegypti salivary glands. An anti-circumsporozoite monoclonal antibody, N2H6D5, whose corresponding heavy- and light-chain gene variable regions were engineered as a single-chain antibody construct, binds to P. gallinaceum sporozoites and prevents infection of Ae. aegypti salivary glands when expressed from a Sindbis virus. Mean intensities of sporozoite infections of salivary glands in mosquitoes expressing N2scFv were reduced as much as 99.9% when compared to controls.

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