Abstract
BackgroundIn Ethiopia, the general population is vulnerable to unpredictable epidemics of Plasmodium falciparum malaria. However, there is little information on the anti-malaria immune profile of the population in the endemic regions of the country.MethodsThe study was designed to investigate the nature of humoral immune response to malaria in two ethnic groups in two endemic localities: Shewa Robit in north, and Boditi in south Ethiopia which are characterized by varying levels of malaria transmission and altitude. In a cross-sectional study, the study participants were diagnosed for malaria infection microscopically and by the rapid diagnostic test (RDT). Sera were tested by using enzyme-linked immunosorbent assay (ELISA) for total immunoglobulin (Ig) G against P. falciparum blood-stage vaccine candidate GMZ2 and its subunits (Glutamate-rich protein (GLURP-R0), merozoite surface protein 3 (MSP3); as well as IgG subclasses against GLURP-R0 and MSP3.ResultsWhereas 23(8.6%) blood smear-positive cases for P. falciparum were detected in Boditi, all Shewa Robit study participants had no detectable P. falciparum infection. In both localities, total IgG prevalence and levels to GMZ2 were significantly higher than the response to the component domains indicating the strong recognition of GMZ2 by antibodies acquired through natural exposure. Total IgG and subclass prevalence and levels were higher in Shewa Robit than Boditi, suggesting difference in the intensity of malaria transmission in the two localities and/or genetic differences between the two populations in their response to the antigens. In both study sites, IgG subclass levels to GLURP-R0 were significantly higher than that to MSP3 for all corresponding subclasses in most individuals, indicating the higher relative antigenicity and probably protective potential of GLURP-R0 compared to MSP3. Against both GLURP-R0 and MSP3, the ratio of cytophilic to noncytophilic antibodies was >1 in the majority of the study participants, in both study sites, suggesting the induction of protective (cytophilic) antibodies against the two antigens. Analysis of age-related pattern in antibody levels against the antigens showed a positive association with increasing age.ConclusionsP. falciparum GLURP-R0 and MSP3 separately as well as in a fused form in GMZ2 are readily recognized by the sera of the study populations. The significantly higher antibody prevalence and level detected against GMZ2 compared to either of its subunits separately, in naturally exposed populations, suggests the synergistic effect of GLURP-R0 and MSP3 and that GMZ2 could be a more relevant blood-stage malaria vaccine candidate than the individual components. Detection of high-level antibody responses in non-febrile, smear-negative individuals may possibly be an indication of a low-grade, asymptomatic sub-microscopic infection in the induction and maintenance of high-level malaria immunity.
Highlights
In Ethiopia, the general population is vulnerable to unpredictable epidemics of Plasmodium falciparum malaria
The significantly higher antibody prevalence and level detected against GMZ2 compared to either of its subunits separately, in naturally exposed populations, suggests the synergistic effect of glutamaterich protein (GLURP)-R0 and MSP3 and that GMZ2 could be a more relevant blood-stage malaria vaccine candidate than the individual components
The present study suggests that both antigens, GLURP-R0 and MSP3, are important for the induction of protective antibodies against malaria from natural infections providing additional rational for combining the two antigens in a hybrid vaccine formulation
Summary
In Ethiopia, the general population is vulnerable to unpredictable epidemics of Plasmodium falciparum malaria. There is little information on the anti-malaria immune profile of the population in the endemic regions of the country. A highly effective malaria vaccine is expected to be a combined multi-stage, multi-component and as such a blood-stage component must be included. Little is understood pertaining to the immune correlates of protection and the appropriate antigens that elicit the relevant immunological machinery. The concern increased when two blood-stage vaccines, falciparum malaria protein 1 representing the 42-kDa C-terminal fragment of merozoite surface protein 1 (MSP1) formulated with AS02 (FMP1/AS02) and apical membrane antigen 1 (AMA1)-C1/Alhydrogel, in Phase IIb trials failed to confer protection despite eliciting high antibody levels [3,4]. Blood-stage parasites are mainly attacked by IgG1 and IgG3 cytophilic, whereas IgG2 and IgG4 noncytophilic may block the protective activity of cytophilic antibodies [6]
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