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Home > Medicine & Health Science textbooks > Medical specialties, branches of medicine > Pathology > Medical microbiology and virology > Biochemical, Functional and Immunogenic Characterisation of the Sars Spike Glycoprotein: Implications for the Development of a Subunit Vaccine(English)
Biochemical, Functional and Immunogenic Characterisation of the Sars Spike Glycoprotein: Implications for the Development of a Subunit Vaccine(English)

Biochemical, Functional and Immunogenic Characterisation of the Sars Spike Glycoprotein: Implications for the Development of a Subunit Vaccine(English)

          
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About the Book

This dissertation, "Biochemical, Functional and Immunogenic Characterisation of the SARS Spike Glycoprotein: Implications for the Development of a Subunit Vaccine" by Yiu-wing, Kam, 甘曜榮, was obtained from The University of Hong Kong (Pokfulam, Hong Kong) and is being sold pursuant to Creative Commons: Attribution 3.0 Hong Kong License. The content of this dissertation has not been altered in any way. We have altered the formatting in order to facilitate the ease of printing and reading of the dissertation. All rights not granted by the above license are retained by the author. Abstract: Abstracts of thesis entitled Biochemical, functional and immunogenic characterisation of the SARS Spike glycoprotein: Implications for the development of a subunit vaccine Submitted by Kam Yiu-wing For the degree of Doctor of Philosophy At The University of Hong Kong in October 2007 Vaccine-induced humoral antibody responses can prevent or aggravate viral infections. I investigated whether a recombinant native full-length S-protein trimer (triSpike) of severe acute respiratory syndrome coronavirus (SARS-CoV) was able to elicit a neutralizing and protective immune response in animals and analyzed the capacity of anti-S antibodies to mediate antibody- dependent enhancement (ADE) of virus entry in vitro and enhancement of replication in vivo. Recombinant triSpike can be expressed in high quantity suggesting that the protein is efficiently produced from our lab-scale production system. The purified triSpike can be obtained in high level of purity suggesting that the immunoaffinity purification process efficiently removes the impurities from the producing cells. Recombinant purified triSpike reacts with human patient sera and binds the ACE2 receptor suggested that the protein is correctly folded and functional. Neutralizing sera prevent binding of the S-protein to ACE2 suggested receptor-binding inhibition as the major mechanism of virus neutralization. SARS-CoV-specific serum and mucosal immunoglobulins were readily detected in immunized animals. Truncated forms of S proteins or glycan-motif modified form of S proteins are inappropriate ways to enhance the immunogenicity of S protein. Serum IgG blocked binding of the S-protein to the ACE2 receptor and neutralized SARS-CoV infection in vitro. However, using SARS-CoV pseudotypes expressing a homologous S-protein we found that neutralizing sera from hamsters and mice facilitated entry of virus in human B cell lines but not in mouse or human macrophages. Entry into human B cell lines occurred in a FcγRII-dependent and ACE2-independent fashion indicated that ADE of virus entry is a novel cell entry mechanism of SARS-CoV. Vaccinated animals showed no signs of enhanced ilung pathology or hepatitis and viral load was undetectable or greatly reduced in lungs when compared with control following challenge with SARS-CoV. Altogether our results indicate that a recombinant trimeric S protein was able to elicit an efficacious and protective immune response in vivo and warrants concern in the safety evaluation of a human vaccine against SARS-CoV. Number of words: 322 ii DOI: 10.5353/th_b3955763 Subjects: Coronaviruses SARS (Disease) - Immunological aspects SARS (Disease) - Vaccination


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Product Details
  • ISBN-13: 9781374664685
  • Publisher: Open Dissertation Press
  • Publisher Imprint: Open Dissertation Press
  • Height: 279 mm
  • No of Pages: 214
  • Spine Width: 11 mm
  • Weight: 508 gr
  • ISBN-10: 1374664685
  • Publisher Date: 27 Jan 2017
  • Binding: Paperback
  • Language: English
  • Series Title: English
  • Sub Title: Implications for the Development of a Subunit Vaccine
  • Width: 216 mm


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Biochemical, Functional and Immunogenic Characterisation of the Sars Spike Glycoprotein: Implications for the Development of a Subunit Vaccine(English)
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