13 research outputs found

    Strain Selection for Generation of O-Antigen-Based Glycoconjugate Vaccines against Invasive Nontyphoidal <i>Salmonella</i> Disease

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    <div><p>Nontyphoidal <i>Salmonellae</i>, principally <i>S</i>. Typhimurium and <i>S</i>. Enteritidis, are a major cause of invasive bloodstream infections in sub-Saharan Africa with no vaccine currently available. Conjugation of lipopolysaccharide O-antigen to a carrier protein constitutes a promising vaccination strategy. Here we describe a rational process to select the most appropriate isolates of <i>Salmonella</i> as source of O-antigen for developing a bivalent glycoconjugate vaccine. We screened a library of 30 <i>S</i>. Typhimurium and 21 <i>S</i>. Enteritidis in order to identify the most suitable strains for large scale O-antigen production and generation of conjugate vaccines. Initial screening was based on growth characteristics, safety profile of the isolates, O-antigen production, and O-antigen characteristics in terms of molecular size, O-acetylation and glucosylation level and position, as determined by phenol sulfuric assay, NMR, HPLC-SEC and HPAEC-PAD. Three animal isolates for each serovar were identified and used to synthesize candidate glycoconjugate vaccines, using CRM<sub>197</sub> as carrier protein. The immunogenicity of these conjugates and the functional activity of the induced antibodies was investigated by ELISA, serum bactericidal assay and flow cytometry. <i>S</i>. Typhimurium O-antigen showed high structural diversity, including O-acetylation of rhamnose in a Malawian invasive strain generating a specific immunodominant epitope. <i>S</i>. Typhimurium conjugates provoked an anti-O-antigen response primarily against the O:5 determinant. O-antigen from <i>S</i>. Enteritidis was structurally more homogeneous than from <i>S</i>. Typhimurium, and no idiosyncratic antibody responses were detected for the <i>S</i>. Enteritidis conjugates. Of the three initially selected isolates, two <i>S</i>. Typhimurium (1418 and 2189) and two <i>S</i>. Enteritidis (502 and 618) strains generated glycoconjugates able to induce high specific antibody levels with high breadth of serovar-specific strain coverage, and were selected for use in vaccine production. The strain selection approach described is potentially applicable to the development of glycoconjugate vaccines against other bacterial pathogens.</p></div

    Epidemiological Transition and the Double Burden of Disease in Accra, Ghana

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    It has long been recognized that as societies modernize, they experience significant changes in their patterns of health and disease. Despite rapid modernization across the globe, there are relatively few detailed case studies of changes in health and disease within specific countries especially for sub-Saharan African countries. This paper presents evidence to illustrate the nature and speed of the epidemiological transition in Accra, Ghana’s capital city. As the most urbanized and modernized Ghanaian city, and as the national center of multidisciplinary research since becoming state capital in 1877, Accra constitutes an important case study for understanding the epidemiological transition in African cities. We review multidisciplinary research on culture, development, health, and disease in Accra since the late nineteenth century, as well as relevant work on Ghana’s socio-economic and demographic changes and burden of chronic disease. Our review indicates that the epidemiological transition in Accra reflects a protracted polarized model. A “protracted” double burden of infectious and chronic disease constitutes major causes of morbidity and mortality. This double burden is polarized across social class. While wealthy communities experience higher risk of chronic diseases, poor communities experience higher risk of infectious diseases and a double burden of infectious and chronic diseases. Urbanization, urban poverty and globalization are key factors in the transition. We explore the structures and processes of these factors and consider the implications for the epidemiological transition in other African cities
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