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Breadth of Anti-Merozoite Antibody Responses Is Associated With the Genetic Diversity of Asymptomatic Plasmodium falciparum Infections and Protection Against Clinical Malaria
Karolinska Institutet, Stockholm, Sweden; KEMRI-Wellcome Trust Research Programme, Centre for Geographical Medicine Research-Coast, Kilifi, Kenya.
KEMRI-Wellcome Trust Research Programme, Centre for Geographical Medicine Research-Coast, Kilifi, Kenya.
Unit of Biostatistics, Department of Epidemiology, Institute of Environmental Medicine, Karolinska Institutet, Stockholm, Sweden.
Örebro University, School of Health and Medical Sciences, Örebro University, Sweden. Örebro University Hospital. Karolinska Institutet, Stockholm, Sweden; Clinical Epidemiology and Biostatistics Unit, Örebro University Hospital, Örebro, Sweden. (Clinical Epidemiology and Biostatistics)ORCID iD: 0000-0001-6328-5494
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2013 (English)In: Clinical Infectious Diseases, ISSN 1058-4838, E-ISSN 1537-6591, Vol. 57, no 10, p. 1409-1416Article in journal (Refereed) Published
Abstract [en]

Background. Elucidating the mechanisms of naturally acquired immunity to Plasmodium falciparum infections would be highly valuable for malaria vaccine development. Asymptomatic multiclonal infections have been shown to predict protection from clinical malaria in a transmission-dependent manner, but the mechanisms underlying this are unclear. We assessed the breadth of antibody responses to several vaccine candidate merozoite antigens in relation to the infecting parasite population and clinical immunity.

Methods. In a cohort study in Tanzania, 320 children aged 1-16 years who were asymptomatic at baseline were included. We genotyped P. falciparum infections by targeting the msp2 gene using polymerase chain reaction and capillary electrophoresis and measured antibodies to 7 merozoite antigens using a multiplex assay. We assessed the correlation between the number of clones and the breadth of the antibody response, and examined their effects on the risk of malaria during 40 weeks of follow-up using age-adjusted multivariate regression models.

Results. The antibody breadth was positively correlated with the number of clones (RR [risk ratio], 1.63; 95% confidence interval [CI], 1.32-2.02). Multiclonal infections were associated with a nonsignificant reduction in the risk of malaria in the absence of antibodies (RR, 0.83; 95% CI, .29-2.34). The breadth of the antibody response was significantly associated with a reduced risk of malaria in the absence of infections (RR, 0.25; 95% CI, .09-.66). In combination, these factors were associated with a lower risk of malaria than they were individually (RR, 0.14; 95% CI, .04-.48). Conclusions. These data suggest that malaria vaccines mimicking naturally acquired immunity should ideally induce antibody responses that can be boosted by natural infections.

Place, publisher, year, edition, pages
2013. Vol. 57, no 10, p. 1409-1416
Keywords [en]
malaria, immunity, multiclonal infections, merozoite surface antigens, antibodies
National Category
Medical and Health Sciences
Identifiers
URN: urn:nbn:se:oru:diva-32532DOI: 10.1093/cid/cit556ISI: 000326292400006OAI: oai:DiVA.org:oru-32532DiVA, id: diva2:667391
Funder
Sida - Swedish International Development Cooperation Agency, SWE-2009-067Wellcome trust, 084538
Note

Funding Agency: Marianne and Marcus Wallenberg Foundation, MMW2010.0067 (se även Forskningsfinansiär)

Available from: 2013-11-26 Created: 2013-11-26 Last updated: 2018-07-22Bibliographically approved

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