Analysis of Hwuoral Immune Response to a Panel of P!aslllodilllllja!cipallllll Blood-Stage Vaccine Candidate Antigens in Nanmtlly Primed Populations in Seasonal Malaria Settings in Ethiopia
No Thumbnail Available
Date
2012-06
Authors
Journal Title
Journal ISSN
Volume Title
Publisher
Addis Ababa University
Abstract
In 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 subclass
Description
Keywords
antigen, blood-stage vaccine, cytophilic IgG subclass, ELISA, Ethiopia, falciparum malaria, noncytophilic IgG subclass