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Infection and Immunity, February 2008, p. 759-766, Vol. 76, No. 2
0019-9567/08/$08.00+0     doi:10.1128/IAI.01147-07
Copyright © 2008, American Society for Microbiology. All Rights Reserved.

Humoral Responses to Plasmodium falciparum Blood-Stage Antigens and Association with Incidence of Clinical Malaria in Children Living in an Area of Seasonal Malaria Transmission in Burkina Faso, West Africa

Centre National de Recherche et de Formation sur le paludisme, Ouagadougou, Burkina Faso,¹ The African Malaria Network Trust, Tanzania Commission for Science and Technology Building, P.O. Box 33207, Dar es Salaam, Tanzania,² Department of Clinical Biochemistry, Statens Serum Institute, Copenhagen, Denmark,³ Noguchi Memorial Institute for Medical Research, University of Ghana, Legon, Ghana,⁴ Department of Parasitology, Biomedical Primate Research Centre, Lange Kleiweg 139, 2288 GJ Rijswijk, The Netherlands,⁵ Ministry of Health, Ghana, P.O. Box M44, Accra, Ghana,⁶ Department of Infectious and Tropical Diseases, London School of Hygiene and Tropical Medicine, Keppel Street, London WC1E 7HT, United Kingdom⁷

Received 18 August 2007/ Returned for modification 4 October 2007/ Accepted 26 November 2007

There is longstanding evidence that immunoglobulin G (IgG) has a role in protection against clinical malaria, and human antibodies of the cytophilic subclasses are thought to be particularly critical in this respect. In this cohort study, 286 Burkinabè children 6 months to 15 years old were kept under malaria surveillance in order to assess the protective role of antibody responses against four antigens which are currently being evaluated as vaccine candidates: apical membrane antigen 1 (AMA1), merozoite surface protein 1-19 (MSP1-19), MSP3, and glutamate-rich protein (GLURP). Total IgG, IgM, and IgG subclass responses were measured just before the malaria transmission season. The incidence of malaria was 2.4 episodes per child year of risk. After adjusting for the confounding effects of age, the level of total IgG to GLURP was strongly associated with reduced malaria incidence (incidence rate ratio associated with a doubling of total IgG, 0.79; 95% confidence interval, 0.66 to 0.94; P = 0.009.); there was a borderline statistically significant association between the level of total IgG to MSP3 and malaria incidence and no evidence of an association for total IgG to AMA1 and to MSP1-19. Of the IgG subclass responses studied, only IgG3 and IgG4 against GLURP and IgG1 against AMA1 were associated with reduced risk of clinical malaria. There was no evidence of an interaction between responses to AMA1 and baseline parasitemia in their effects on malaria incidence. Currently included in malaria vaccine formulations for clinical trials in humans, these blood-stage antigens, AMA1 and GLURP, offer good prospects for malaria vaccine development.

Published ahead of print on 10 December 2007.

Editor: W. A. Petri, Jr.

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