Document Detail


Characterization of anti-var2CSA-PfEMP1 cytoadhesion inhibitory mouse monoclonal antibodies.
MedLine Citation:
PMID:  17095277     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
Pregnancy-associated malaria (PAM) is associated with the massive sequestration of erythrocytes infected with CSA-binding parasites in the placenta. Natural protective immunity against PAM is acquired during the course of pregnancies, with the development of anti-PfEMP1 antibodies recognizing placental infected erythrocytes (IEs) from different geographical regions. Mouse monoclonal antibodies (mabs) were raised against Plasmodium falciparum variant surface proteins expressed by CSA-binding parasites. These mabs blocked 0-60% of CSA-binding parasite adhesion and immunoprecipitated a 350 kDa 125I-labeled PfEMP1(CSA). Two var2CSA domains expressed on the surface of CHO cells (DBL5epsilon and DBL6epsilon) were identified as the targets of three of four antibodies inhibiting CSA binding. Two of these antibodies also recognized either DBL2x or DBL3x, suggesting that some epitopes may be common to several var2CSA domains. These mabs also specifically selected CSA-binding IEs and facilitated the purification from IE extracts of the native var2CSA ligand. This purified ligand elicited antibodies in immunized mice inhibiting efficiently IE(CSA) cytoadhesion. Based on our findings, we provide the first demonstration that the parasite var2CSA surface protein can elicit inhibitory antibodies and define here the subunits of the var2CSA ligand suitable for use in vaccine development.
Authors:
Marion Avril; Benoit Gamain; Catherine Lépolard; Nicolas Viaud; Artur Scherf; Jürg Gysin
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Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't     Date:  2006-10-17
Journal Detail:
Title:  Microbes and infection / Institut Pasteur     Volume:  8     ISSN:  1286-4579     ISO Abbreviation:  Microbes Infect.     Publication Date:    2006 Nov-Dec
Date Detail:
Created Date:  2006-12-18     Completed Date:  2007-04-02     Revised Date:  -    
Medline Journal Info:
Nlm Unique ID:  100883508     Medline TA:  Microbes Infect     Country:  France    
Other Details:
Languages:  eng     Pagination:  2863-71     Citation Subset:  IM    
Affiliation:
Unité de Parasitologie Expérimentale, URA Institut Pasteur, Univ Med. EA 3282, IFR 48 Université de la Méditerranée 27, Bd. Jean Moulin, 13385, Marseille Cedex 05, France.
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MeSH Terms
Descriptor/Qualifier:
Animals
Antibodies, Monoclonal / immunology*
Antibodies, Protozoan / immunology*
Antibody Specificity
Antigens, Protozoan / chemistry,  immunology*,  metabolism
CHO Cells / metabolism
Chondroitin Sulfates / metabolism
Cricetinae
Cricetulus
Erythrocytes / parasitology
Humans
Mice
Placenta / parasitology
Plasmodium falciparum / chemistry,  physiology
Protein Binding / immunology
Protein Structure, Tertiary
Chemical
Reg. No./Substance:
0/Antibodies, Monoclonal; 0/Antibodies, Protozoan; 0/Antigens, Protozoan; 0/VAR2CSA protein, Plasmodium falciparum; 9007-28-7/Chondroitin Sulfates

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