Petros Beyene (Professor)Mamo Hassen2018-07-022023-11-082018-07-022023-11-082012-06http://etd.aau.edu.et/handle/123456789/5497In Ethiopia, the general population is quite vulnerable to unpredictable cyclic epidemics of Plasmodium falciparum malaria. However, there is very little information on the anti-malaria immune profile of the population residing in the endemic regions of the country. This study was designed to investigate the nature of humoral immune response to malaria in two population groups in two endemic localities, Shewa Robit in the north and Boditi in south. In a cross-sectional study, the study participants were diagnosed for malaria infection microscopically and by the rapid diagnostic test (RDT). The sera were tested by using enzyme-linked immunosorbent assay (ELISA) for total immunoglobulin (Ig) G against P. falciparum blood-stage vaccine candidate antigens: apical membrane antigen 1 (AMA1), glutamate-rich protein (GLURP) R2 region, and merozoite surface protein 2 (MSP2) allelic variants (3D7 and FC27) in Shewa Robit. Total IgG against GLURP-R0, MSP3 and GMZ2 and IgG subclasses against GLURP-R0 and MSP3 were assayed in both Shewa Robit and Boditi sera. Whereas 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. At both localities total IgG prevalence and levels to GMZ2 were significantly higher than the response to the component domains (GLURP-R0 and MSP3) indicating the induction of strong GMZ2-specific natural antibodies. There was significant difference between the median antibody level to GMZ2, GLURP-R0 and MSP3 compared to the responses to other antigens tested in Shewa Robit, indicating that GMZ2 could be a more relevant blood-stage malaria vaccine candidate antigen. Higher total IgG and subclass prevalence and levels were detected in Shewa Robit than Boditi, suggesting difference in the intensity of malaria transmission in the two localities and/or genetic differences between the two population groups in their response to blood-stage P. falciparum antigens. In both study sites, IgG subclass antibody levels to GLURP-R0 were significantly higher than that to MSP3 for all corresponding subclasses in most individuals, indicating the higher relative immunogenicity and 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, indicating the induction of protective antibodies against the two antigens. Analysis of age-related pattern in antibody levels against the antigens tested showed a positive association with increasing age for most antigens suggesting the role of intrinsic agerelated factors in immune maturation. The age factor appears plausible as there was no evidence for increase in antibody response with increasing frequency of reported past clinical malaria. Overall, the study has shown that Ethiopian population groups residing in unstable and seasonal malaria epidemiological settings have a high prevalence and levels of long-lived antibodies that readily recognize P. falciparum blood-stage vaccine candidate antigens, particularly GMZ2 and its component fractions (GLURP-R0 and MSP3). Furthermore, detection of high level antibody responses in non-febrile smear-negative individuals without history of reported past malaria episodes may possibly be an indication of a low-grade, asymptomatic (submicroscopic) infections in the induction and maintenance of high level protective immunity. Therefore, to determine the implication of submicroscopic infections in the induction and boosting of malaria immunity versus the existence of long-lived malaria-specific antibodies in the absence of boosting from submicroscopic infection, PCR confirmation of the microscopy-negative samples would be necessary. Keywords: antigen, blood-stage vaccine, cytophilic IgG subclass, ELISA, Ethiopia, falciparum malaria, noncytophilic IgG subclassenantigenblood-stage vaccinecytophilic IgG subclassELISAEthiopia, falciparum malarianoncytophilic IgG subclassThesis