Measurement of the plasma levels of antibodies against the polymorphic vaccine candidate apical membrane antigen 1 in a malaria-exposed population
1 Department of Parasitology, Biomedical Primate Research Centre, Postbox 3306, 2280, GH Rijswijk, The Netherlands
2 Department of Immunology, Noguchi Memorial Institute for Medical Research, College of Health Sciences, University of Ghana, P.O. Box LG581, Legon, Accra, Ghana
3 Department of Biostatistics, School of Public Health, University of Ghana, P. O. Box LG13, Legon, Accra, Ghana
BMC Infectious Diseases 2012, 12:32 doi:10.1186/1471-2334-12-32Published: 2 February 2012
Establishing antibody correlates of protection against malaria in human field studies and clinical trials requires, amongst others, an accurate estimation of antibody levels. For polymorphic antigens such as apical membrane antigen 1 (AMA1), this may be confounded by the occurrence of a large number of allelic variants in nature.
To test this hypothesis, plasma antibody levels in an age-stratified cohort of naturally exposed children from a malaria-endemic area in Southern Ghana were determined by indirect ELISA. Titres against four single PfAMA1 alleles were compared with those against three different allele mixtures presumed to have a wider repertoire of epitope specificities. Associations of antibody levels with the incidence of clinical malaria as well as with previous exposure to parasites were also examined.
Antibody titres against PfAMA1 alleles generally increased with age/exposure while antibody specificity for PfAMA1 variants decreased, implying that younger children (≤ 5 years) elicit a more strain-specific antibody response compared to older children. Antibody titre measurements against the FVO and 3D7 AMA1 alleles gave the best titre estimates as these varied least in pair-wise comparisons with titres against all PfAMA1 allele mixtures. There was no association between antibody levels against any capture antigen and either clinical malaria incidence or parasite density.
The current data shows that levels of naturally acquired antigen-specific antibodies, especially in infants and young children, are dependent on the antigenic allele used for measurement. This may be relevant to the interpretation of antibody titre data from measurements against single PfAMA1 alleles, especially in studies involving infants and young children who have experienced fewer infections.