This Article
Right arrow Full Text
Right arrow Full Text (PDF)
Right arrow Alert me when this article is cited
Right arrow Alert me if a correction is posted
Services
Right arrow Similar articles in this journal
Right arrow Similar articles in PubMed
Right arrow Alert me to new issues of the journal
Right arrow Download to citation manager
Right arrowReprints and Permissions
Right arrow Copyright Information
Right arrow Books from ASM Press
Right arrow MicrobeWorld
Citing Articles
Right arrow Citing Articles via HighWire
Right arrow Citing Articles via Google Scholar
Google Scholar
Right arrow Articles by Bir, N.
Right arrow Articles by Chitnis, C. E.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Bir, N.
Right arrow Articles by Chitnis, C. E.

 Previous Article  |  Next Article 

Infection and Immunity, October 2006, p. 5955-5963, Vol. 74, No. 10
0019-9567/06/$08.00+0     doi:10.1128/IAI.00481-06
Copyright © 2006, American Society for Microbiology. All Rights Reserved.

Immunogenicity of Duffy Binding-Like Domains That Bind Chondroitin Sulfate A and Protection against Pregnancy-Associated Malaria

Nivedita Bir,1 Syed Shams Yazdani,1 Marion Avril,2 Corinne Layez,2 Jürg Gysin,2 and Chetan E. Chitnis1*

Malaria Group, International Centre for Genetic Engineering, and Biotechnology (ICGEB), New Delhi 110067, India,1 Unité de Parasitologie Expérimentale, Faculté de Médecine, Université de la Méditerranée, Marseille, France2

Received 24 March 2006/ Returned for modification 4 June 2006/ Accepted 3 July 2006

Sequestration of Plasmodium falciparum-infected erythrocytes in the placenta is implicated in pathological outcomes of pregnancy-associated malaria (PAM). P. falciparum isolates that sequester in the placenta primarily bind chondroitin sulfate A (CSA). Following exposure to malaria during pregnancy, women in areas of endemicity develop immunity, and so multigravid women are less susceptible to PAM than primigravidae. Protective immunity to PAM is associated with the development of antibodies that recognize diverse CSA-binding, placental P. falciparum isolates. The epitopes recognized by such protective antibodies have not been identified but are likely to lie in conserved Duffy binding-like (DBL) domains, encoded by var genes, that bind CSA. Immunization of mice with the CSA-binding DBL3{gamma} domain encoded by var1CSA elicits cross-reactive antibodies that recognize diverse CSA-binding P. falciparum isolates and block their binding to placental cryosections under flow. However, CSA-binding isolates primarily express var2CSA, which does not encode any DBL{gamma} domains. Here, we demonstrate that antibodies raised against DBL3{gamma} encoded by var1CSA cross-react with one of the CSA-binding domains, DBL3X, encoded by var2CSA. This explains the paradoxical observation made here and earlier that anti-rDBL3{gamma} sera recognize CSA-binding isolates and provides evidence for the presence of conserved, cross-reactive epitopes in diverse CSA-binding DBL domains. Such cross-reactive epitopes within CSA-binding DBL domains can form the basis for a vaccine that provides protection against PAM.

* Corresponding author. Mailing address: Malaria Group, International Centre for Genetic Engineering and Biotechnology (ICGEB), Aruna Asaf Ali Marg, New Delhi 110067, India. Phone and fax: 91 11 2618 7695. E-mail: cchitnis{at}icgeb.res.in.

Editor: J. L. Flynn

Infection and Immunity, October 2006, p. 5955-5963, Vol. 74, No. 10
0019-9567/06/$08.00+0     doi:10.1128/IAI.00481-06
Copyright © 2006, American Society for Microbiology. All Rights Reserved.



This article has been cited by other articles:

  • Mayor, A., Rovira-Vallbona, E., Srivastava, A., Sharma, S. K., Pati, S. S., Puyol, L., Quinto, L., Bassat, Q., Machevo, S., Mandomando, I., Chauhan, V. S., Alonso, P. L., Chitnis, C. E. (2009). Functional and Immunological Characterization of a Duffy Binding-Like Alpha Domain from Plasmodium falciparum Erythrocyte Membrane Protein 1 That Mediates Rosetting. Infect. Immun. 77: 3857-3863 [Abstract] [Full Text]  
  • Vigan-Womas, I., Guillotte, M., Le Scanf, C., Igonet, S., Petres, S., Juillerat, A., Badaut, C., Nato, F., Schneider, A., Lavergne, A., Contamin, H., Tall, A., Baril, L., Bentley, G. A., Mercereau-Puijalon, O. (2008). An In Vivo and In Vitro Model of Plasmodium falciparum Rosetting and Autoagglutination Mediated by varO, a Group A var Gene Encoding a Frequent Serotype. Infect. Immun. 76: 5565-5580 [Abstract] [Full Text]  


Copyright © 2009 by the American Society for Microbiology.   For an alternate route to Journals.ASM.org, visit: http://intl-journals.asm.org | More Info»