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PMID: 16088838 Published · ppublish English Journal Article Research Support, N.I.H., Extramural Research Support, Non-U.S. Gov't Research Support, U.S. Gov't, P.H.S.

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

The Journal of infectious diseases ·Vol. 192 ·No. 5 ·2005-09-01 ·Pages 878-87

Li F, Patra KP, Vinetz JM

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.

MeSH Terms
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
Chemicals
Antibodies, Protozoan Protozoan Proteins RNA, Messenger Recombinant Proteins Chitinases pfCHT1, chitinase
Authors & Affiliations
3 authors, click to expand affiliations / ORCID
Li Fengwu
Division of Infectious Diseases, Department of Medicine, University of California-San Diego School of Medicine, La Jolla, California 92093-0640, USA.
Patra Kailash P
Vinetz Joseph M
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Article Info
Journal
The Journal of infectious diseases
Abbr.
J Infect Dis
ISSN
0022-1899
DOI
10.1086/432552
Published
2005-09-01
Epub
2005-00-27
Pages
878-87
Language
English
Region
United States
NLM ID
0413675
PMCID
PMC2265778
Subset
IM
Grants
NHLBI NIH HHS · 5P01HL066941 · United States
NIAID NIH HHS · K02 AI050049 · United States
NIAID NIH HHS · K02AI50049 · United States
NCRR NIH HHS · 5U42RR005991 · United States
NCRR NIH HHS · U42 RR005991 · United States
NHLBI NIH HHS · P01 HL066941 · United States
NIAID NIH HHS · R01 AI045999 · United States
NIAID NIH HHS · R01AI45999 · United States
NIAID NIH HHS · R01 AI045999-06A2 · United States
NIAID NIH HHS · K02 AI050049-05 · United States
External Links
PubMed source DOI: 10.1086/432552 PMC Full Text View journal details
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