Abstract
BackgroundNaturally acquired immunity to clinical malaria is thought to be mainly antibody-mediated, but reports on antigen targets are contradictory. Recognition of multiple antigens may be crucial for protection. In this study, the magnitude of antibody responses and their temporal stability was assessed for a panel of malaria antigens in relation to protection against clinical Plasmodium falciparum malaria.MethodsMalian children aged two to 14 years were enrolled in a longitudinal study and followed up by passive and active case detection for seven months. Plasma was collected at enrolment and at the beginning, in the middle and after the end of the transmission season. Antibody titres to the P. falciparum-antigens apical membrane protein (AMA)-1, merozoite surface protein (MSP)-119, MSP-3, glutamine-rich protein (GLURP-R0) and circumsporozoite antigen (CSP) were assessed by enzyme-linked immunosorbent assay (ELISA) for 99 children with plasma available at all time points. Parasite carriage was determined by microscopy and nested PCR.ResultsAntibody titres to all antigens, except MSP-119, and the number of antigens recognized increased with age. After malaria exposure, antibody titres increased in children that had low titres at baseline, but decreased in those with high baseline responses. No significant differences were found between antibody titers for individual antigens between children remaining symptomatic or asymptomatic after exposure, after adjustment for age. Instead, children remaining asymptomatic following parasite exposure had a broader repertoire of antigen recognition.ConclusionsThe present study provides immune-epidemiological evidence from a limited cohort of Malian children that strong recognition of multiple antigens, rather than antibody titres for individual antigens, is associated with protection from clinical malaria.Electronic supplementary materialThe online version of this article (doi:10.1186/s12936-015-0567-9) contains supplementary material, which is available to authorized users.
Highlights
Acquired immunity to clinical malaria is thought to be mainly antibody-mediated, but reports on antigen targets are contradictory
Association of antibody titres and breadth of the humoral response with age and parasitaemia A longitudinal study was performed in 99 children during one malaria transmission season in Samako, a village in a hyperendemic area of Mali
The number of clinical malaria episodes recorded during longitudinal follow-up of this cohort from July to Dec 2012 peaked in October (July n = 1, Aug n = 8, Sept n = 9, Oct n = 19, Nov n = 17, Dec n = 4)
Summary
Acquired immunity to clinical malaria is thought to be mainly antibody-mediated, but reports on antigen targets are contradictory. The magnitude of antibody responses and their temporal stability was assessed for a panel of malaria antigens in relation to protection against clinical Plasmodium falciparum malaria. Despite the success of major public health control efforts in recent years [1], malaria remains one of the most important causes of morbidity and mortality in the world with an estimated 207 million cases and 627,000 deaths in 2012 [2]. Antibody-mediated immune responses to malaria antigens help to control blood-stage parasitaemia and have a protective effect on clinical disease, as shown in passive transfer experiments [3,4].
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