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.MethodsWe 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.ResultsAntibodies 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.ConclusionsGrowth inhibitory activity was significantly associated with breadth of antibody reactivity to merozoite antigens, encouraging the prospect of a multicomponent blood-stage vaccine.
Highlights
MethodsWe 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
Plasmodium falciparum uses a repertoire of merozoite-stage proteins for invasion of erythrocytes
Growth inhibitory activity was significantly associated with breadth of antibody reactivity to merozoite antigens, encouraging the prospect of a multicomponent blood-stage vaccine
Summary
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. Children aged between 2 and 14 years with P falciparum slidepositive clinical malaria were recruited in 3 ecologically distinct areas in Ghana: (1) Ledzokuku-Krowor municipality (LEKMA) in Accra, (2) Kassena and Nankana districts in northern Ghana, and (3) Kintampo Municipality in the middle belt of Ghana, as described in detail elsewhere [16, 17]. Informed written assent was obtained from children between 12 and 17 years of age. Venous blood from (1) children with malaria confirmed by rapid diagnostic test and microscopy and (2) healthy adults with no recent history of malaria was collected into tubes containing acid citrate dextrose, from which plasma was obtained
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