Antibody Reactivity to Merozoite Antigens in Ghanaian Adults Correlates With Growth Inhibitory Activity Against Plasmodium falciparum in Culture

Author:

Mensah-Brown Henrietta E12,Aspeling-Jones Harvey3,Delimini Rupert K4,Asante Kwaku Poku5,Amlabu Emmanuel16,Bah Saikou Y12,Beeson James G78,Wright Gavin J9,Conway David J3,Awandare Gordon A12

Affiliation:

1. West African Centre for Cell Biology of Infectious Pathogens, University of Ghana, Legon, Accra, Ghana

2. Department of Biochemistry, Cell and Molecular Biology, University of Ghana, Legon, Accra, Ghana

3. London School of Hygiene and Tropical Medicine, London, United Kingdom

4. Department of Biomedical Sciences, University of Health and Allied Sciences, Ho, Ghana

5. Kintampo Health Research Center, Kintampo, Ghana

6. Department of Biochemistry, Kogi State University, Anyigba, Nigeria

7. The Burnet Institute for Medical Research and Public Health, Melbourne, Australia

8. Department of Microbiology, Monash University, Clayton, Australia

9. Pathogens and Microbes Programme, Wellcome Trust Sanger Institute, United Kingdom

Abstract

Abstract Background Plasmodium falciparum uses a repertoire of merozoite-stage proteins for invasion of erythrocytes. Antibodies against some of these proteins halt the replication cycle of the parasite by preventing erythrocyte invasion and are implicated as contributors to protective immunity against malaria. Methods We assayed antibody reactivity against a panel of 9 recombinant antigens based on erythrocyte-binding antigen (EBA) and reticulocyte-like homolog (Rh) proteins in plasma from children with malaria and healthy adults residing in 3 endemic areas in Ghana using enzyme-linked immunosorbent assay. Purified immunoglobulin (Ig)G from adult plasma samples was also tested for invasion inhibition against 7 different P falciparum culture lines, including clinical isolates. Results Antibodies against the antigens increased in an age-dependent manner in children. Breadth of reactivity to the different antigens was strongly associated with in vitro parasite growth inhibitory activity of IgG purified from the adults. The strongest predictors of breadth of antibody reactivity were age and transmission intensity, and a combination of reactivities to Rh2, Rh4, and Rh5 correlated strongly with invasion inhibition. Conclusions Growth inhibitory activity was significantly associated with breadth of antibody reactivity to merozoite antigens, encouraging the prospect of a multicomponent blood-stage vaccine.

Funder

Royal Society

World Bank African Centres of Excellence

Wellcome Trust DELTAS/African Academy of Science

National Institutes of Health/National Institute of Allergy and Infectious Diseases

Wellcome Trust

Publisher

Oxford University Press (OUP)

Subject

Infectious Diseases,Oncology

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