Reduction of malaria transmission by transgenic mosquitoes expressing an antisporozoite antibody in their salivary glands

We have previously developed a robust salivary gland‐specific expression system in transgenic Anopheles stephensi mosquitoes. To establish transgenic mosquito lines refractory to Plasmodium falciparum using this system, we generated a transgenic mosquito harbouring the gene encoding an anti‐P. falci...

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Published inInsect molecular biology Vol. 22; no. 1; pp. 41 - 51
Main Authors Sumitani, M., Kasashima, K., Yamamoto, D. S., Yagi, K., Yuda, M., Matsuoka, H., Yoshida, S.
Format Journal Article
LanguageEnglish
Published England Blackwell Publishing Ltd 01.02.2013
Subjects
Animals
Animals, Genetically Modified
Anopheles - genetics
Anopheles - parasitology
Cell Line - drug effects
Cell Line - parasitology
circumsporozoite protein
Disease Models, Animal
malaria
Malaria - parasitology
Malaria - transmission
Mice
Mice, Inbred ICR
Molecular Sequence Data
Plasmodium falciparum - genetics
Plasmodium falciparum - growth & development
Protozoan Proteins - genetics
Protozoan Proteins - immunology
Protozoan Proteins - metabolism
salivary glands
Salivary Glands - physiology
Single-Chain Antibodies - genetics
Single-Chain Antibodies - immunology
Single-Chain Antibodies - pharmacology
single-chain antibody fragment
transgenic mosquito
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Summary:We have previously developed a robust salivary gland‐specific expression system in transgenic Anopheles stephensi mosquitoes. To establish transgenic mosquito lines refractory to Plasmodium falciparum using this system, we generated a transgenic mosquito harbouring the gene encoding an anti‐P. falciparum circumsporozoite protein (PfCSP) single‐chain antibody (scFv) fused to DsRed in a secretory form (mDsRed‐2A10 scFv). Fluorescence microscopy showed that the mDsRed‐2A10 scFv was localized in the secretory cavities and ducts of the salivary glands in a secreted form. To evaluate P. falciparum transmission‐blocking in a rodent malaria model, a transgenic Plasmodium berghei line expressing PfCSP in place of PbCSP (PfCSP/Pb) was constructed. The PfCSP/Pb parasites were able to bind to the mDsRed‐2A10 scFv in the salivary glands of the transgenic mosquitoes. Importantly, the infectivity of the transgenic mosquitoes to mice was strongly impaired, indicating that the parasites had been inactivated. These results suggest that salivary gland‐specific expression of antisporozoite molecules could be a promising strategy for blocking malaria transmission to humans.
Bibliography:istex:1A6D881436BB949208DBA2B9CA847C195228AF68
Grant-in-Aid for Scientific Research (B) - No. 21390126
Figure S1. The DNA sequence and its deduced amino acid sequence of the variable region of light chain (VL) and heavy chain (VH). Nucleotide numbers are shown on the left.Figure S2. Fluorescence microscopy (upper) and transmission (lower) images of the salivary glands of a transgenic mosquito. (A, C) Salivary gland from a 1-day-old transgenic female mosquito. (B, D) Salivary gland from a male transgenic mosquito. Scale bar = 100 μm. (E) Detection of the mDsRed-2A10 scFv in a 1-day-old adult transgenic mosquito. A 56-kDa band was detected in salivary glands, but not in carcasses following salivary gland removal.Table S1. (A) Number of wild-type (WT) mosquitoes fed on individual naïve mice. (B) Number of transgenic (TG) mosquitoes fed on individual naïve mice.Supplemental material. The DNA sequence of the aappP-mDsRed-2A10scFv-Antryp1 gene cassette.
Grant-in-Aid for Young Scientists (B) - No. 22790398
ArticleID:IMB1168
ark:/67375/WNG-WGT05NDC-T
ObjectType-Article-1
SourceType-Scholarly Journals-1
ObjectType-Feature-2
content type line 23
ISSN:0962-1075
1365-2583
DOI:10.1111/j.1365-2583.2012.01168.x