Abstract
Background Differences in parasite transmission intensity influence the process of acquisition of host immunity to Plasmodium falciparum malaria and ultimately, the rate of malaria related morbidity and mortality. Potential vaccines being designed to complement current intervention efforts therefore need to be evaluated against different malaria endemicity backgrounds.MethodsThe associations between antibody responses to the chimeric merozoite surface protein 1 block 2 hybrid (MSP1 hybrid), glutamate-rich protein region 2 (GLURP R2) and the peptide AS202.11, and the risk of malaria were assessed in children living in malaria hyperendemic (Burkina Faso, n = 354) and hypo-endemic (Ghana, n = 209) areas. Using the same reagent lots and standardized protocols for both study sites, immunoglobulin (Ig) M, IgG and IgG sub-class levels to each antigen were measured by ELISA in plasma from the children (aged 6–72 months). Associations between antibody levels and risk of malaria were assessed using Cox regression models adjusting for covariates.ResultsThere was a significant association between GLURP R2 IgG3 and reduced risk of malaria after adjusting age of children in both the Burkinabe (hazard ratio 0.82; 95 % CI 0.74–0.91, p < 0.0001) and the Ghanaian (HR 0.48; 95 % CI 0.25–0.91, p = 0.02) cohorts. MSP1 hybrid IgM was associated (HR 0.85; 95 % CI 0.73–0.98, p = 0.02) with reduced risk of malaria in Burkina Faso cohort while IgG against AS202.11 in the Ghanaian children was associated with increased risk of malaria (HR 1.29; 95 % CI 1.01–1.65, p = 0.04).ConclusionThese findings support further development of GLURP R2 and MSP1 block 2 hybrid, perhaps as a fusion vaccine antigen targeting malaria blood stage that can be deployed in areas of varying transmission intensity.Electronic supplementary materialThe online version of this article (doi:10.1186/s12936-016-1146-4) contains supplementary material, which is available to authorized users.
Highlights
Differences in parasite transmission intensity influence the process of acquisition of host immunity to Plasmodium falciparum malaria and the rate of malaria related morbidity and mortality
This synthetic protein was immunogenic in experimental animal models and was recognized by sera from Burkinabe and Ghanaian children naturally exposed to the parasite [8]; studies assessing anti-merozoite surface protein 1 (MSP1) block 2 hybrid antibodies in relation to the risk of malaria in longitudinal cohorts is currently lacking
This study successfully evaluated the associations between antibody responses against GLURP glutamate rich protein region 2 (R2), MSP1 block 2 hybrid and the peptide AS202.11 and the risk of malaria in two populations (Burkina Faso and Ghana) with different malaria transmission intensities
Summary
Differences in parasite transmission intensity influence the process of acquisition of host immunity to Plasmodium falciparum malaria and the rate of malaria related morbidity and mortality. Antibody responses targeting polymorphic malaria parasite surface proteins have been associated with reduced risk of malaria [4,5,6] This may partly explain the need for repeated infections in the acquisition of natural protective immunity among adults living in endemic populations [7]. A synthetic MSP1 block 2 construct, based on several polymorphic variants found in natural Plasmodium falciparum isolates was designed and fused with the relatively conserved block 1 sequence of MSP1 to form the MSP1 block 2 hybrid [8] This synthetic protein was immunogenic in experimental animal models and was recognized by sera from Burkinabe and Ghanaian children naturally exposed to the parasite [8]; studies assessing anti-MSP1 block 2 hybrid antibodies in relation to the risk of malaria in longitudinal cohorts is currently lacking
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