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Infection and Immunity, September 2009, p. 3857-3863, Vol. 77, No. 9
0019-9567/09/$08.00+0 doi:10.1128/IAI.00049-09
Copyright © 2009, American Society for Microbiology. All Rights Reserved.
Functional and Immunological Characterization of a Duffy Binding-Like Alpha Domain from Plasmodium falciparum Erythrocyte Membrane Protein 1 That Mediates Rosetting 
Alfredo Mayor,1,2,3*
Eduard Rovira-Vallbona,1
Anand Srivastava,2
Surya K. Sharma,4
Sudhanshu S. Pati,5
Laura Puyol,1
Llorenç Quinto,1
Quique Bassat,1,3
Sonia Machevo,3
Inacio Mandomando,3
Virander S. Chauhan,2
Pedro L. Alonso,1,3 and
Chetan E. Chitnis2
Barcelona Centre for International Health Research (CRESIB), Hospital Clínic/Institut d'Investigacions Biomèdiques August Pi i Sunyer (IDIBAPS), Universitat de Barcelona, Barcelona, Spain,1 International Centre for Genetic Engineering and Biotechnology, Aruna Asaf Ali Marg, New Delhi, India,2 Manhiça Health Research Centre (CISM), Maputo, Mozambique,3 National Institute of Malaria Research (formerly Malaria Research Centre), Field Station, Sector 5, Rourkela, District Sundargarh, Orissa, India,4 Ispat General Hospital, Rourkela, District Sundargarh, Orissa, India5
Received 15 January 2009/ Returned for modification 12 February 2009/ Accepted 5 June 2009
The Duffy binding-like (DBL) domains are common adhesion modules present in Plasmodium falciparum erythrocyte membrane protein 1 (PfEMP1) variants, which are responsible for immune evasion and cytoadherence. Knowledge about how immune responses are acquired against polymorphic DBL domains of PfEMP1 can aid in the development of vaccines for malaria. A recombinant DBL
domain, encoded by R29 var1, which binds complement receptor 1 to mediate rosetting by the P. falciparum laboratory strain R29, was expressed in Escherichia coli, renatured by oxidative refolding to its native form, and purified to homogeneity. Antibody levels in 704 plasmas obtained from residents of areas of different levels of malaria endemicity in Orissa (India) and Manhiça (Mozambique) were assessed by enzyme-linked immunosorbent assay. The refolded DBL domain was pure, homogeneous, and functional in that it bound human erythrocytes with specificity and was capable of inhibiting rosetting. The proportion of individuals who had measurable anti-DBL immunoglobulin G responses was low in areas of low malaria endemicity in Orissa (6.7%) but high in areas of high endemicity in Orissa (87.5%) and Manhiça (74.5%). Seroprevalence and antibody levels against the recombinant protein increased with the age of inhabitants from areas with high transmission rates (P < 0.001). Half of the children in these areas had seroconverted by the age of 5 years. These findings suggest that in spite of the extreme polymorphism of PfEMP1 DBL domains, the acquisition of specific antibodies is rapid and age related and reflects the reduced risk of malaria in areas with high transmission rates. Further studies are required to elucidate the role of these antibodies in protection from malaria.
* Corresponding author. Mailing address: Barcelona Centre for International Health Research (CRESIB), Hospital Clínic/Universitat de Barcelona, Rosselló 132, 08036 Barcelona, Spain. Phone: 34.932275706. Fax: 34.932279853. E-mail: agmayor{at}clinic.ub.es
Published ahead of print on 22 June 2009.
Infection and Immunity, September 2009, p. 3857-3863, Vol. 77, No. 9
0019-9567/09/$08.00+0 doi:10.1128/IAI.00049-09
Copyright © 2009, American Society for Microbiology. All Rights Reserved.
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