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Glycoengineered hepatitis B virus-like particles with enhanced immunogenicity.
Joe, Carina C D; Chatterjee, Sayantani; Lovrecz, George; Adams, Timothy E; Thaysen-Andersen, Morten; Walsh, Renae; Locarnini, Stephen A; Smooker, Peter; Netter, Hans J.
Afiliação
  • Joe CCD; Royal Melbourne Institute of Technology (RMIT) University, School of Science, Melbourne, Victoria 3001, Australia; Commonwealth Scientific and Industrial Research Organisation, Clayton, Victoria 3169, Australia.
  • Chatterjee S; Department of Molecular Sciences, Macquarie University, Sydney, New South Wales 2109, Australia.
  • Lovrecz G; Commonwealth Scientific and Industrial Research Organisation, Clayton, Victoria 3169, Australia.
  • Adams TE; Commonwealth Scientific and Industrial Research Organisation, Clayton, Victoria 3169, Australia.
  • Thaysen-Andersen M; Department of Molecular Sciences, Macquarie University, Sydney, New South Wales 2109, Australia.
  • Walsh R; Victorian Infectious Diseases Reference Laboratory (VIDRL), Melbourne Health, The Peter Doherty Institute, Melbourne, Victoria 3000, Australia.
  • Locarnini SA; Victorian Infectious Diseases Reference Laboratory (VIDRL), Melbourne Health, The Peter Doherty Institute, Melbourne, Victoria 3000, Australia.
  • Smooker P; Royal Melbourne Institute of Technology (RMIT) University, School of Science, Melbourne, Victoria 3001, Australia.
  • Netter HJ; Royal Melbourne Institute of Technology (RMIT) University, School of Science, Melbourne, Victoria 3001, Australia; Victorian Infectious Diseases Reference Laboratory (VIDRL), Melbourne Health, The Peter Doherty Institute, Melbourne, Victoria 3000, Australia. Electronic address: hans.netter@mh.org.au
Vaccine ; 38(22): 3892-3901, 2020 05 08.
Article em En | MEDLINE | ID: mdl-32284273
Virus-like particles (VLP) represent biological platforms for the development of novel products such as vaccines and delivery platforms for foreign antigenic sequences. VLPs composed of the small surface antigen (HBsAgS) derived from the hepatitis B virus (HBV) are the immunogenic components of a licensed, preventative vaccine, which contains aluminum hydroxide as adjuvant. Herein, we report that glycoengineering of N-glycosylated HBsAgS to generate hyper-glycosylated VLPs display an enhanced immunogenicity relative to the wild type (WT) HBsAgS VLPs when expressed in FreeStyle HEK 293F cells. Comparative mass spectrometry-based N-glycan profiling, gel electrophoresis, and immunoassays demonstrated that WT and hyper-glycosylated HBsAgS VLPs contain the same type and distribution of N-glycan structures, but the latter shows a higher glycan abundance per protein mass. The antigenic integrity of the modified VLPs was also shown to be retained. To assess whether hyper-glycosylated VLPs induce an enhanced immune response in the presence of the adjuvant aluminum hydroxide, the anti-HBV surface antigen (anti-HBsAgS) antibody response was monitored in BALB/c mice, subcutaneously injected with different VLP derivatives. In the absence and presence of adjuvant, hyper-glycosylated VLPs showed an enhanced immunogenicity compared to WT VLPs. The ability of hyper-glycosylated VLPs to promote potent anti-HBsAgS immune responses compared to VLPs with a native N-glycan level as well as non-glycosylated, yeast-derived HBsAgS VLPs opens exciting avenues for generating more efficacious VLP-based vaccines against hepatitis B and improved HBsAgS VLP carrier platforms using glycoengineering.
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Texto completo: 1 Base de dados: MEDLINE Assunto principal: Vacinas contra Hepatite B / Vacinas de Partículas Semelhantes a Vírus / Imunogenicidade da Vacina / Hepatite B Limite: Animals Idioma: En Revista: Vaccine Ano de publicação: 2020 Tipo de documento: Article País de afiliação: Austrália

Texto completo: 1 Base de dados: MEDLINE Assunto principal: Vacinas contra Hepatite B / Vacinas de Partículas Semelhantes a Vírus / Imunogenicidade da Vacina / Hepatite B Limite: Animals Idioma: En Revista: Vaccine Ano de publicação: 2020 Tipo de documento: Article País de afiliação: Austrália