Antigenic characterization of an intrinsically unstructured protein, Plasmodium falciparum merozoite surface protein 2.

Abstract:

:Merozoite surface protein 2 (MSP2) is an abundant glycosylphosphatidylinositol (GPI)-anchored protein of Plasmodium falciparum, which is a potential component of a malaria vaccine. As all forms of MSP2 can be categorized into two allelic families, a vaccine containing two representative forms of MSP2 may overcome the problem of diversity in this highly polymorphic protein. Monomeric recombinant MSP2 is an intrinsically unstructured protein, but its conformational properties on the merozoite surface are unknown. This question is addressed here by analyzing the 3D7 and FC27 forms of recombinant and parasite MSP2 using a panel of monoclonal antibodies raised against recombinant MSP2. The epitopes of all antibodies, mapped using both a peptide array and by nuclear magnetic resonance (NMR) spectroscopy on full-length recombinant MSP2, were shown to be linear. The antibodies revealed antigenic differences, which indicate that the conserved N- and C-terminal regions, but not the central variable region, are less accessible in the parasite antigen. This appears to be an intrinsic property of parasite MSP2 and is not dependent on interactions with other merozoite surface proteins as the loss of some conserved-region epitopes seen using the immunofluorescence assay (IFA) on parasite smears was also seen on Western blot analyses of parasite lysates. Further studies of the structural basis of these antigenic differences are required in order to optimize recombinant MSP2 constructs being evaluated as potential vaccine components.

journal_name

Infect Immun

journal_title

Infection and immunity

authors

Adda CG,MacRaild CA,Reiling L,Wycherley K,Boyle MJ,Kienzle V,Masendycz P,Foley M,Beeson JG,Norton RS,Anders RF

doi

10.1128/IAI.00665-12

subject

Has Abstract

pub_date

2012-12-01 00:00:00

pages

4177-85

issue

12

eissn

0019-9567

issn

1098-5522

pii

IAI.00665-12

journal_volume

80

pub_type

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