Browsing by Author "Nebie, I."
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Item Antibodies to malaria vaccine candidates are associated with chloroquine or sulphadoxine/pyrimethamine treatment efficacy in children in an endemic area of Burkina Faso(Malaria Journal, 2012-03) Diarra, A.; Nebie, I.; Tiono, A.; Soulama, I.; Ouedraogo, A.; Konate, A.; Theisen, M.; Dodoo, D.; Traore, A.; Sirima, S.B.Background: Patient immune status is thought to affect the efficacy of anti-malarial chemotherapy. This is a subject of some importance, since evidence of immunity-related interactions may influence our use of chemotherapy in populations with drug resistance, as well as assessment of the value of suboptimal vaccines. The study aim was to investigate relationship between antibodies and anti-malarial drug treatment outcomes. Methods. Some 248 children aged 0.5 and 15 years were recruited prior to the high malaria transmission season. Venous blood (5 ml) was obtained from each child to measure antibody levels to selected malaria antigens, using ELISA. Blood smears were also performed to assess drug efficacy and malaria infection prevalence. Children were actively followed up to record clinical malaria cases. Results: IgG levels to MSP3 were always higher in the successfully treated group than in the group with treatment failure. The same observation was made for GLURP but the reverse observation was noticed for MSP1-19. Cytophilic and non-cytophilic antibodies were significantly associated with protection against all three antigens, except for IgG4 to MSP1-19 and GLURP. Conclusion: Acquired anti-malarial antibodies may play an important role in the efficacy of anti-malarial drugs in younger children more susceptible to the disease. © 2012 Diarra et al; licensee BioMed Central Ltd.Item Antibody levels against GLURP R2, MSP1 block 2 hybrid and AS202.11 and the risk of malaria in children living in hyperendemic (Burkina Faso) and hypo-endemic (Ghana) areas(BioMed Central Ltd, 2016) Adu, B.; Cherif, M.K.; Bosomprah, S.; Diarra, A.; Arthur, F.K.N.; Dickson, E.K.; Corradin, G.; Cavanagh, D.R.; Theisen, M.; Sirima, S.B.; Nebie, I.; Dodoo, D.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. Methods: The 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. Results: There 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). Conclusion: These 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. © 2016 Adu et al.Item Humoral responses to plasmodium falciparum blood-stage antigens and association with incidence of clinical malaria in children living in an area of seasonal malaria transmission in Burkina Faso, West Africa.(2007-12-10) Nebie, I.; Diarra, A.; Ouedraogo, A.; Bosomprah, S.; Bougouma, E.C.; Tiono, A.B.; Konate, A.T.; Chilengi, R.; Theisen, M.; Dodoo, D.; Remarque, E.; Milligan, P.; Sirima, S.B.There is longstanding evidence that immunoglobulin G (IgG) has a role in protection against clinical malaria, and human antibodies of the cytophilic subclasses are thought to be particularly critical in this respect. In this cohort study, 286 Burkinabè children 6 months to 15 years old were kept under malaria surveillance in order to assess the protective role of antibody responses against four antigens which are currently being evaluated as vaccine candidates: apical membrane antigen 1 (AMA1), merozoite surface protein 1-19 (MSP1-19), MSP3, and glutamate-rich protein (GLURP). Total IgG, IgM, and IgG subclass responses were measured just before the malaria transmission season. The incidence of malaria was 2.4 episodes per child year of risk. After adjusting for the confounding effects of age, the level of total IgG to GLURP was strongly associated with reduced malaria incidence (incidence rate ratio associated with a doubling of total IgG, 0.79; 95% confidence interval, 0.66 to 0.94; P = 0.009.); there was a borderline statistically significant association between the level of total IgG to MSP3 and malaria incidence and no evidence of an association for total IgG to AMA1 and to MSP1-19. Of the IgG subclass responses studied, only IgG3 and IgG4 against GLURP and IgG1 against AMA1 were associated with reduced risk of clinical malaria. There was no evidence of an interaction between responses to AMA1 and baseline parasitemia in their effects on malaria incidence. Currently included in malaria vaccine formulations for clinical trials in humans, these blood-stage antigens, AMA1 and GLURP, offer good prospects for malaria vaccine development. Copyright © 2008, American Society for Microbiology. All Rights Reserved.Item Naturally acquired antibody responses to recombinant Pfs230 and Pfs48/45 transmission blocking vaccine candidates(Journal of Infection, 2015-07) Jones, S.; Grignard, L.; Nebie, I.; Chilongola, J.; Dodoo, D.; Sauerwein, R.; Theisen, M.; Roeffen, W.; Singh, S.K.; Singh, R.K.; Singh, S.; Kyei-Baafour, E.; Tetteh, K.; Drakeley, C.; Bousema, T.Objectives: Pfs48/45 and Pfs230 are Plasmodium falciparum sexual stage proteins and promising malaria transmission-blocking vaccine candidates. Antibody responses against these proteins may be naturally acquired and target antigens may be under selective pressure. This has consequences for the future evaluation of vaccine immunogenicity and efficacy in populations naturally exposed to malaria. Methods: We determined naturally acquired antibody responses to the recombinant proteins Pfs48/45-10C and Pfs230-230CMB in children from three malaria endemic settings in Ghana, Tanzania and Burkina Faso. We also examined genetic polymorphisms in the P. falciparum gene pfs48/45. Results: Antibody prevalence was 1.1-18.2% for 10C and 6.7-18.9% for 230CMB. In Burkina Faso we observed evidence of an age-dependent acquisition pattern for both 10C (p<0.001) and 230CMB (p=0.031). Membrane feeding assays on a separate dataset demonstrated an association between functional transmission reducing activity and antibody prevalence for both 10C (p=0.017) and 230CMB (p=0.049). 17 single nucleotide polymorphisms were found in pfs48/45 (from 126 samples), with 5 non-synonymous SNPs in the Pfs48/45 10C region. Conclusions: We conclude there are naturally acquired antibody responses to both vaccine candidates which have functional relevance by reducing the transmissibility of infected individuals. We identified genetic polymorphisms, in pfs48/45 which exhibited geographical specificity. © 2015 The British Infection Association.