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      Comparative Antibody Responses Against three Antimalarial Vaccine Candidate Antigens from Urban and Rural Exposed Individuals in Gabon

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          Abstract

          The analysis of immune responses in diverse malaria endemic regions provides more information to understand the host’s immune response to Plasmodium falciparum. Several plasmodial antigens have been reported as targets of human immunity. PfAMA1 is one of most studied vaccine candidates; PfRH5 and Pf113 are new promising vaccine candidates. The aim of this study was to evaluate humoral response against these three antigens among children of Lastourville (rural area) and Franceville (urban area). Malaria was diagnosed using rapid diagnosis tests. Plasma samples were tested against these antigens by enzyme-linked immunosorbent assay (ELISA). We found that malaria prevalence was five times higher in the rural area than in the urban area ( p < 0.0001). The anti-PfAMA1 and PfRh5 response levels were significantly higher in Lastourville than in Franceville ( p < 0.0001; p = 0.005). The anti-AMA1 response was higher than the anti-Pf113 response, which in turn was higher than the anti-PfRh5 response in both sites. Anti-PfAMA1 levels were significantly higher in infected children than those in uninfected children ( p = 0.001) in Franceville. Anti-Pf113 and anti-PfRh5 antibody levels were lowest in children presenting severe malarial anemia. These three antigens are targets of immunity in Gabon. Further studies on the role of Pf113 in antimalarial protection against severe anemia are needed.

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          Most cited references45

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          Gamma-globulin and acquired immunity to human malaria.

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            A field trial to assess a blood-stage malaria vaccine.

            Blood-stage malaria vaccines are intended to prevent clinical disease. The malaria vaccine FMP2.1/AS02(A), a recombinant protein based on apical membrane antigen 1 (AMA1) from the 3D7 strain of Plasmodium falciparum, has previously been shown to have immunogenicity and acceptable safety in Malian adults and children. In a double-blind, randomized trial, we immunized 400 Malian children with either the malaria vaccine or a control (rabies) vaccine and followed them for 6 months. The primary end point was clinical malaria, defined as fever and at least 2500 parasites per cubic millimeter of blood. A secondary end point was clinical malaria caused by parasites with the AMA1 DNA sequence found in the vaccine strain. The cumulative incidence of the primary end point was 48.4% in the malaria-vaccine group and 54.4% in the control group; efficacy against the primary end point was 17.4% (hazard ratio for the primary end point, 0.83; 95% confidence interval [CI], 0.63 to 1.09; P=0.18). Efficacy against the first and subsequent episodes of clinical malaria, as defined on the basis of various parasite-density thresholds, was approximately 20%. Efficacy against clinical malaria caused by parasites with AMA1 corresponding to that of the vaccine strain was 64.3% (hazard ratio, 0.36; 95% CI, 0.08 to 0.86; P=0.03). Local reactions and fever after vaccination were more frequent with the malaria vaccine. On the basis of the primary end point, the malaria vaccine did not provide significant protection against clinical malaria, but on the basis of secondary results, it may have strain-specific efficacy. If this finding is confirmed, AMA1 might be useful in a multicomponent malaria vaccine. (Funded by the National Institute of Allergy and Infectious Diseases and others; ClinicalTrials.gov number, NCT00460525.).
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              Identification and prioritization of merozoite antigens as targets of protective human immunity to Plasmodium falciparum malaria for vaccine and biomarker development.

              The development of effective malaria vaccines and immune biomarkers of malaria is a high priority for malaria control and elimination. Ags expressed by merozoites of Plasmodium falciparum are likely to be important targets of human immunity and are promising vaccine candidates, but very few Ags have been studied. We developed an approach to assess Ab responses to a comprehensive repertoire of merozoite proteins and investigate whether they are targets of protective Abs. We expressed 91 recombinant proteins, located on the merozoite surface or within invasion organelles, and screened them for quality and reactivity to human Abs. Subsequently, Abs to 46 proteins were studied in a longitudinal cohort of 206 Papua New Guinean children to define Ab acquisition and associations with protective immunity. Ab responses were higher among older children and those with active parasitemia. High-level Ab responses to rhoptry and microneme proteins that function in erythrocyte invasion were identified as being most strongly associated with protective immunity compared with other Ags. Additionally, Abs to new or understudied Ags were more strongly associated with protection than were Abs to current vaccine candidates that have progressed to phase 1 or 2 vaccine trials. Combinations of Ab responses were identified that were more strongly associated with protective immunity than responses to their single-Ag components. This study identifies Ags that are likely to be key targets of protective human immunity and facilitates the prioritization of Ags for further evaluation as vaccine candidates and/or for use as biomarkers of immunity in malaria surveillance and control.

                Author and article information

                Journal
                Eur J Microbiol Immunol (Bp)
                Eur J Microbiol Immunol (Bp)
                EUJMI
                European Journal of Microbiology & Immunology
                Akadémiai Kiadó (Budapest )
                2062-509X
                2062-8633
                03 November 2016
                01 December 2016
                : 6
                : 4
                : 287-297
                Affiliations
                [1 ]Unité de Parasitologie Médicale (UPARAM), Centre International de Recherches Médicales de Franceville (CIRMF) , BP 769 Franceville, Gabon
                [2 ]Molécules de Communication et Adaptation des Microorganismes (MCAM, UMR 7245), Sorbonne Universités, Muséum National d’Histoire Naturelle, CNRS, CP52 , 57 rue Cuvier 75005 Paris, France
                [3 ]Ecole Doctorale Régionale en Infectiologie Tropicale d’Afrique Centrale (ECODRAC) , BP 876 Franceville, Gabon
                [4 ]Laboratoire de Recherches en Immunologie, Parasitologie et Microbiologie, Ecole Doctorale Régionale en Infectiologie Tropicale d’Afrique Centrale (ECODRAC) , BP 876 Franceville, Gabon
                [5 ]Wellcome Trust Sanger Institute , Cambridge CB10 1HH, UK
                [6 ] Département de Parasitologie-Mycologie, Université des Sciences de la Santé , BP 4008 Libreville, Gabon
                Author notes
                * Unité de Parasitologie Médicale (UPARAM), Centre International de Recherches Médicales de Franceville (CIRMF), BP 769 Franceville, Gabon; lekana_jb@ 123456yahoo.fr

                + These authors contributed equally to the article.

                Article
                10.1556/1886.2016.00027
                5146647
                0a2159cf-cc61-482b-8538-69d62fdccc6e
                © 2016, The Author(s)

                This is an Open Access article distributed under the terms of the Creative Commons Attribution Non-Commercial License ( http://creativecommons.org/licenses/by-nc/3.0/) which permits unrestricted non-commercial use, distribution, and reproduction in any medium, provided the original work is properly cited.

                History
                : 20 July 2016
                : 15 August 2016
                Page count
                Figures: 5, Tables: 2, Equations: 0, References: 51, Pages: 11
                Funding
                Funding sources: The study was funded by the Centre International de Recherches Médicales de Franceville (CIRMF, Gabon) and the Agence Universitaire de la Francophonie (AUF). This work was supported by a Wellcome Trust grant (number 098051).
                Categories
                Original Article

                p. falciparum,antibodies,vaccine candidates,pf ama1,pf113,pfrh5,gabon

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