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O-acetylation of typhoid capsular polysaccharide confers polysaccharide rigidity and immunodominance by masking additional epitopes.
Hitri, Krisztina; Kuttel, Michelle M; De Benedetto, Gianluigi; Lockyer, Kay; Gao, Fang; Hansal, Peter; Rudd, Timothy R; Beamish, Emma; Rijpkema, Sjoerd; Ravenscroft, Neil; Bolgiano, Barbara.
Afiliación
  • Hitri K; Division of Bacteriology, National Institute for Biological Standards and Control (NIBSC), Blanche Lane, South Mimms, Potters Bar, Hertfordshire EN6 3QG, UK.
  • Kuttel MM; Department of Computer Science, University of Cape Town, Private Bag X3, Rondebosch, 7701 Cape Town, South Africa.
  • De Benedetto G; Division of Bacteriology, National Institute for Biological Standards and Control (NIBSC), Blanche Lane, South Mimms, Potters Bar, Hertfordshire EN6 3QG, UK.
  • Lockyer K; Division of Bacteriology, National Institute for Biological Standards and Control (NIBSC), Blanche Lane, South Mimms, Potters Bar, Hertfordshire EN6 3QG, UK.
  • Gao F; Division of Bacteriology, National Institute for Biological Standards and Control (NIBSC), Blanche Lane, South Mimms, Potters Bar, Hertfordshire EN6 3QG, UK.
  • Hansal P; Division of Bacteriology, National Institute for Biological Standards and Control (NIBSC), Blanche Lane, South Mimms, Potters Bar, Hertfordshire EN6 3QG, UK.
  • Rudd TR; Laboratory of Molecular Structure, Analytical and Biological Sciences, NIBSC, Blanche Lane, South Mimms, Potters Bar, Hertfordshire EN6 3QG, UK.
  • Beamish E; Division of Bacteriology, National Institute for Biological Standards and Control (NIBSC), Blanche Lane, South Mimms, Potters Bar, Hertfordshire EN6 3QG, UK.
  • Rijpkema S; Division of Bacteriology, National Institute for Biological Standards and Control (NIBSC), Blanche Lane, South Mimms, Potters Bar, Hertfordshire EN6 3QG, UK.
  • Ravenscroft N; Department of Chemistry, University of Cape Town, Private Bag X3, Rondebosch, 7701 Cape Town, South Africa.
  • Bolgiano B; Division of Bacteriology, National Institute for Biological Standards and Control (NIBSC), Blanche Lane, South Mimms, Potters Bar, Hertfordshire EN6 3QG, UK. Electronic address: Barbara.Bolgiano@nibsc.org.
Vaccine ; 37(29): 3866-3875, 2019 06 27.
Article en En | MEDLINE | ID: mdl-31160100
In this work, we explore the effects of O-acetylation on the physical and immunological characteristics of the WHO International Standards of Vi polysaccharide (Vi) from both Citrobacter freundii and Salmonella enterica serovar Typhi. We find that, although structurally identical according to NMR, the two Vi standards have differences with respect to susceptibility to de-O-acetylation and viscosity in water. Vi standards from both species have equivalent mass and O-acetylation-dependent binding to a mouse monoclonal antibody and to anti-Vi polyclonal antisera, including the WHO International Standard for human anti-typhoid capsular Vi PS IgG. This study also confirms that human anti-Vi sera binds to completely de-O-acetylated Vi. Molecular dynamics simulations provide conformational rationales for the known effect of de-O-acetylation both on the viscosity and antigenicity of the Vi, demonstrating that de-O-acetylation has a very marked effect on the conformation and dynamic behavior of the Vi, changing the capsular polysaccharide from a rigid helix into a more flexible coil, as well as enhancing the strong interaction of the polysaccharide with sodium ions. Partial de-O-acetylation of Vi revealed hidden epitopes that were recognized by human and sheep anti-Vi PS immune sera. These findings have significance for the manufacture and evaluation of Vi vaccines.
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Polisacáridos Bacterianos / Vacunas Tifoides-Paratifoides / Epítopos Inmunodominantes Tipo de estudio: Prognostic_studies Límite: Humans Idioma: En Revista: Vaccine Año: 2019 Tipo del documento: Article Pais de publicación: Países Bajos
Texto completo
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Imprimir
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Polisacáridos Bacterianos / Vacunas Tifoides-Paratifoides / Epítopos Inmunodominantes Tipo de estudio: Prognostic_studies Límite: Humans Idioma: En Revista: Vaccine Año: 2019 Tipo del documento: Article Pais de publicación: Países Bajos