Cohort study of the association of antibody levels to AMA1, MSP119, MSP3 and GLURP with protection from clinical malaria in Ghanaian children

被引:114
作者
Dodoo, Daniel [1 ]
Aikins, Anastasia [1 ]
Kusi, Kwadwo Asamoah [1 ,2 ]
Lamptey, Helena [1 ]
Remarque, Ed [2 ]
Milligan, Paul [3 ]
Bosomprah, Samuel [4 ]
Chilengi, Roma [5 ]
Osei, Yaa Difie [6 ]
Akanmori, Bartholomew Dicky [1 ]
Theisen, Michael [7 ]
机构
[1] Univ Ghana, Noguchi Mem Inst Med Res, Legon, Ghana
[2] Biomed Primate Res Ctr, Dept Parasitol, NL-2288 GJ Rijswijk, Netherlands
[3] Univ London London Sch Hyg & Trop Med, Dept Infect & Trop Dis, London WC1E 7HT, England
[4] Minist Hlth, Accra, Ghana
[5] African Malaria Network Trust, Dar Es Salaam, Tanzania
[6] Univ Ghana, Dept Biochem, Legon, Ghana
[7] State Serum Inst, Dept Infect Dis Immunol, Copenhagen, Denmark
基金
英国医学研究理事会; 英国惠康基金;
关键词
D O I
10.1186/1475-2875-7-142
中图分类号
R51 [传染病];
学科分类号
100401 ;
摘要
natural protection against clinical malaria, but conflicting estimates of this association have emerged from immuno-epidemiological studies in different geographical settings. This study was aimed at assessing in a standardized manner the relationship between the antibody responses to four malaria vaccine candidate antigens and protection from clinical malaria, in a cohort of Ghanaian children. Methods: Standardized ELISA protocols were used to measure isotype and IgG subclass levels to Apical Membrane Antigen 1 (AMA1), Merozoite Surface Protein 1-19 (MSP119), Merozoite Surface Protein 3 (MSP3) and Glutamate Rich Protein (GLURP) antigens in plasma samples from 352 Ghanaian children, aged three to 10 years with subsequent malaria surveillance for nine months. This is one of a series of studies in different epidemiological settings using the same standardized ELISA protocols to permit comparisons of results from different laboratories. Results: The incidence rate of malaria was 0.35 episodes per child per year. Isotype and IgG subclasses for all antigens investigated increased with age, while the risk of malaria decreased with age. After adjusting for age, higher levels of IgG to GLURP, MSP1(19), MSP3 and IgM to MSP1(19), MSP3 and AMA1 were associated with decreased malaria incidence. Of the IgG subclasses, only IgG1 to MSP1(19) was associated with reduced incidence of clinical malaria. A previous study in the same location failed to find an association of antibodies to MSP1(19) with clinical malaria. The disagreement may be due to differences in reagents, ELISA and analytical procedures used in the two studies. When IgG, IgM and IgG subclass levels for all four antigens were included in a combined model, only IgG1 [( 0.80 (0.67-0.97), p = 0.018)] and IgM [(0.48 (0.32-0.72), p < 0.001)] to MSP1(19) were independently associated with protection from malaria. Conclusion: Using standardized procedures, the study has confirmed the importance of antibodies to MSP1(19) in reducing the risk of clinical malaria in Ghanaian children, thus substantiating its potential as a malaria vaccine candidate.
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页数:11
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