An anti-Chitinase malaria transmission-blocking single-chain antibody as an effector molecule for creating a Plasmodium falciparum-refractory mosquito.

Abstract	Indirect evidence has suggested the existence of a second chitinase gene, PgCHT2, in the avian malaria parasite Plasmodium gallinaceum. We have now identified PgCHT2 as the orthologue of the P. falciparum chitinase gene PfCHT1, a malaria transmission-blocking target. Computational phylogenetic evidence and biochemical and cell biological functional data support the hypothesis that an avian-related Plasmodium species was the ancestor of both P. falciparum and P. reichenowi, and this single lineage gave rise to another lineage of malaria parasites, including P. vivax, P. knowlesi, P. berghei, P. yoelii, and P. chabaudi. A recombinant PfCHT1/PgCHT2-neutralizing single-chain antibody significantly reduced P. falciparum and P. gallinaceum parasite transmission to mosquitoes. This single-chain antibody is the first anti-P. falciparum effector molecule to be validated for making a malaria transmission-refractory transgenic Anopheles species mosquito. P. gallinaceum is a relevant animal model that facilitates a mechanistic understanding of P. falciparum invasion of the mosquito midgut.
Authors	Fengwu Li, Kailash P Patra, Joseph M Vinetz
Journal	The Journal of infectious diseases (J Infect Dis) Vol. 192 Issue 5 Pg. 878-87 (Sep 01 2005) ISSN: 0022-1899 [Print] United States
PMID	16088838 (Publication Type: Journal Article, Research Support, N.I.H., Extramural, Research Support, Non-U.S. Gov't, Research Support, U.S. Gov't, P.H.S.)
Chemical References	Antibodies, Protozoan Protozoan Proteins RNA, Messenger Recombinant Proteins Chitinases pfCHT1, chitinase
Topics	Aedes (parasitology) Amino Acid Sequence Animals Anopheles (parasitology) Antibodies, Protozoan (genetics, immunology) Base Sequence Biological Assay Chitinases (genetics, immunology) Malaria, Avian (parasitology, prevention & control, transmission) Malaria, Falciparum (parasitology, transmission) Molecular Sequence Data Phylogeny Plasmodium falciparum (enzymology, genetics) Plasmodium gallinaceum (enzymology, genetics) Protozoan Proteins RNA, Messenger (chemistry, genetics) Recombinant Proteins (genetics) Reverse Transcriptase Polymerase Chain Reaction

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