A Longitudinal Study of Type-Specific Antibody Responses toPlasmodiumfalciparumMerozoite Surface Protein-1 in an Area of Unstable Malaria in Sudan

Author:

Cavanagh David R.1,Elhassan Ibrahim M.2,Roper Cally1,Robinson V. Jane1,Giha Haider3,Holder Anthony A.4,Hviid Lars5,Theander Thor G.5,Arnot David E.1,McBride Jana S.1

Affiliation:

1. *Institute of Cell, Animal and Population Biology, Division of Biological Sciences, University of Edinburgh, Edinburgh, Scotland, United Kingdom;

2. †Institute of Endemic Diseases and

3. ‡Department of Biochemistry, University of Khartoum, Sudan;

4. ¶National Institute for Medical Research, The Ridgeway, London, United Kingdom

5. §Centre for Medical Parasitology at Institute of Medical Microbiology and Immunology, University of Copenhagen, and Department of Infectious Diseases, Copenhagen University Hospital, Copenhagen, Denmark; and

Abstract

AbstractMerozoite surface protein-1 (MSP-1) of Plasmodium falciparum is a malaria vaccine candidate Ag. Immunity to MSP-1 has been implicated in protection against infection in animal models. However, MSP-1 is a polymorphic protein and its immune recognition by humans following infection is not well understood. We have compared the immunogenicity of conserved and polymorphic regions of MSP-1, the specificity of Ab responses to a polymorphic region of the Ag, and the duration of these responses in Sudanese villagers intermittently exposed to P. falciparum infections. Recombinant Ags representing the conserved N terminus (Block 1), the conserved C terminus, and the three main types of the major polymorphic region (Block 2) of MSP-1 were used to determine the specificity and longitudinal patterns of IgG Ab responses to MSP-1 in individuals. Abs from 52 donors were assessed before, during, and after malaria transmission seasons for 4 yr. Ags from the Block 1 region were rarely recognized by any donor. Responses to the C-terminal Ag occurred in the majority of acutely infected individuals and thus were a reliable indicator of recent clinical infection. Ags from the polymorphic Block 2 region of MSP-1 were recognized by many, although not all individuals after clinical malaria infections. Responses to Block 2 were type specific and correlated with PCR typing of parasites present at the time of infection. Responses to all of these Ags declined within a few months of drug treatment and parasite clearance, indicating that naturally induced human Ab responses to MSP-1 are short lived.

Publisher

The American Association of Immunologists

Subject

Immunology,Immunology and Allergy

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