Research

Acquisition of naturally occurring antibody responses to recombinant protein domains of Plasmodium falciparum erythrocyte membrane protein 1

Claire L Mackintosh^1,2,3 , Zoe Christodoulou² , Tabitha W Mwangi¹ , Moses Kortok¹ , Robert Pinches² , Thomas N Williams^1,3,4 , Kevin Marsh^1,2,3 and Christopher I Newbold^2,3

¹  Kenya Medical Research Institute Centre for Geographic Medicine Research Coast (KEMRI-CGMRC), Kilifi District Hospital, Kilifi, Kenya

²  Molecular Parasitology Group, Weatherall Institute of Molecular Medicine, John Radcliffe Hospital, Oxford, UK

³  Nuffield Department of Medicine, John Radcliffe Hospital, Oxford, UK

⁴  Department of Paediatrics, John Radcliffe Hospital, Oxford, UK

author email corresponding author email

Malaria Journal 2008, 7:155doi:10.1186/1475-2875-7-155

Published:	16 August 2008

Abstract

Background

Antibodies targeting variant antigens expressed on the surface of Plasmodium falciparum infected erythrocytes have been associated with protection from clinical malaria. The precise target for these antibodies is unknown. The best characterized and most likely target is the erythrocyte surface-expressed variant protein family Plasmodium falciparum erythrocyte membrane protein 1 (PfEMP1).

Methods

Using recombinant proteins corresponding to five domains of the expressed A4 var gene, A4 PfEMP1, the naturally occurring antibody response was assessed, by ELISA, to each domain in serum samples obtained from individuals resident in two communities of differing malaria transmission intensity on the Kenyan coast. Using flow cytometry, the correlation in individual responses to each domain with responses to intact A4-infected erythrocytes expressing A4 PfEMP1 on their surface as well as responses to two alternative parasite clones and one clinical isolate was assessed.

Results

Marked variability in the prevalence of responses between each domain and between each transmission area was observed, as wasa strong correlation between age and reactivity with some but not all domains. Individual responses to each domain varied strikingly, with some individuals showing reactivity to all domains and others with no reactivity to any, this was apparent at all age groups. Evidence for possible cross-reactivity in responses to the domain DBL4γ was found.

Conclusion

Individuals acquire antibodies to surface expressed domains of a highly variant protein. The finding of potential cross-reactivity in responses to one of these domains is an important initial finding in the consideration of potential vaccine targets.