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  1. NTU Theses and Dissertations Repository
  2. 醫學院
  3. 國際三校農業生技與健康醫療碩士學位學程
請用此 Handle URI 來引用此文件: http://tdr.lib.ntu.edu.tw/jspui/handle/123456789/80969
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dc.contributor.advisor姜至剛(Chih-Kang Chiang)
dc.contributor.authorHan-Yi Huangen
dc.contributor.author黃菡頤zh_TW
dc.date.accessioned2022-11-24T03:24:08Z-
dc.date.available2021-10-01
dc.date.available2022-11-24T03:24:08Z-
dc.date.copyright2021-10-01
dc.date.issued2021
dc.date.submitted2021-09-09
dc.identifier.citation1 Worldometers.info. Coronavirus Update (Live) https://www.worldometers.info/coronavirus/. 2 WHO. Draft landscape and tracker of COVID-19 candidate vaccines https://www.who.int/publications/m/item/draft-landscape-of-covid-19-candidate-vaccines. 3 Craven, J. COVID-19 Vaccine Tracker https://www.raps.org/news-and-articles/news-articles/2020/3/covid-19-vaccine-tracker, 2021). 4 Pollard, A. J. Bijker, E. M. A guide to vaccinology: from basic principles to new developments. Nature Reviews Immunology 21, 83-100, doi:10.1038/s41577-020-00479-7 (2021). 5 Callaway, E. The race for coronavirus vaccines: a graphical guide. Nature 580, 576-577, doi:10.1038/d41586-020-01221-y (2020). 6 Zhang, Y. et al. Safety, tolerability, and immunogenicity of an inactivated SARS-CoV-2 vaccine in healthy adults aged 18–59 years: a randomised, double-blind, placebo-controlled, phase 1/2 clinical trial. The Lancet Infectious Diseases 21, 181-192, doi:10.1016/S1473-3099(20)30843-4 (2021). 7 Xia, S. et al. Effect of an Inactivated Vaccine Against SARS-CoV-2 on Safety and Immunogenicity Outcomes: Interim Analysis of 2 Randomized Clinical Trials. Jama 324, 951-960, doi:10.1001/jama.2020.15543 (2020). 8 Ella, R. et al. Safety and immunogenicity of an inactivated SARS-CoV-2 vaccine, BBV152: interim results from a double-blind, randomised, multicentre, phase 2 trial, and 3-month follow-up of a double-blind, randomised phase 1 trial. Lancet Infect Dis 21, 950-961, doi:10.1016/s1473-3099(21)00070-0 (2021). 9 Voysey, M. et al. Safety and efficacy of the ChAdOx1 nCoV-19 vaccine (AZD1222) against SARS-CoV-2: an interim analysis of four randomised controlled trials in Brazil, South Africa, and the UK. The Lancet 397, 99-111, doi:https://doi.org/10.1016/S0140-6736(20)32661-1 (2021). 10 Sadoff, J. et al. Interim Results of a Phase 1-2a Trial of Ad26.COV2.S Covid-19 Vaccine. N Engl J Med 384, 1824-1835, doi:10.1056/NEJMoa2034201 (2021). 11 Zhu, F.-C. et al. Safety, tolerability, and immunogenicity of a recombinant adenovirus type-5 vectored COVID-19 vaccine: a dose-escalation, open-label, non-randomised, first-in-human trial. The Lancet 395, 1845-1854, doi:https://doi.org/10.1016/S0140-6736(20)31208-3 (2020). 12 Baden, L. R. et al. Efficacy and Safety of the mRNA-1273 SARS-CoV-2 Vaccine. N Engl J Med 384, 403-416, doi:10.1056/NEJMoa2035389 (2021). 13 Polack, F. P. et al. Safety and Efficacy of the BNT162b2 mRNA Covid-19 Vaccine. N Engl J Med 383, 2603-2615, doi:10.1056/NEJMoa2034577 (2020). 14 Garcia-Beltran, W. F. et al. Multiple SARS-CoV-2 variants escape neutralization by vaccine-induced humoral immunity. Cell, doi:https://doi.org/10.1016/j.cell.2021.03.013 (2021). 15 Korber, B. et al. Tracking Changes in SARS-CoV-2 Spike: Evidence that D614G Increases Infectivity of the COVID-19 Virus. Cell 182, 812-827.e819, doi:https://doi.org/10.1016/j.cell.2020.06.043 (2020). 16 Zou, J. et al. The effect of SARS-CoV-2 D614G mutation on BNT162b2 vaccine-elicited neutralization. npj Vaccines 6, 44, doi:10.1038/s41541-021-00313-8 (2021). 17 Weissman, D. et al. D614G Spike Mutation Increases SARS CoV-2 Susceptibility to Neutralization. Cell Host Microbe 29, 23-31.e24, doi:10.1016/j.chom.2020.11.012 (2021). 18 Davies, N. G. et al. Estimated transmissibility and impact of SARS-CoV-2 lineage B.1.1.7 in England. Science 372, eabg3055, doi:10.1126/science.abg3055 (2021). 19 Rambaut, A. et al. A dynamic nomenclature proposal for SARS-CoV-2 lineages to assist genomic epidemiology. Nature Microbiology 5, 1403-1407, doi:10.1038/s41564-020-0770-5 (2020). 20 Wang, G. L. et al. Susceptibility of Circulating SARS-CoV-2 Variants to Neutralization. N Engl J Med, doi:10.1056/NEJMc2103022 (2021). 21 Wang, P. et al. Antibody resistance of SARS-CoV-2 variants B.1.351 and B.1.1.7. Nature 593, 130-135, doi:10.1038/s41586-021-03398-2 (2021). 22 Supasa, P. et al. Reduced neutralization of SARS-CoV-2 B.1.1.7 variant by convalescent and vaccine sera. Cell 184, 2201-2211.e2207, doi:https://doi.org/10.1016/j.cell.2021.02.033 (2021). 23 Garcia-Beltran, W. F. et al. Multiple SARS-CoV-2 variants escape neutralization by vaccine-induced humoral immunity. Cell 184, 2372-2383.e2379, doi:10.1016/j.cell.2021.03.013 (2021). 24 Shinde, V. et al. Efficacy of NVX-CoV2373 Covid-19 Vaccine against the B.1.351 Variant. The New England journal of medicine 384, 1899-1909, doi:10.1056/NEJMoa2103055 (2021). 25 Zhou, D. et al. Evidence of escape of SARS-CoV-2 variant B.1.351 from natural and vaccine-induced sera. Cell 184, 2348-2361.e2346, doi:https://doi.org/10.1016/j.cell.2021.02.037 (2021). 26 Tseng, Y. C. et al. Egg-based influenza split virus vaccine with monoglycosylation induces cross-strain protection against influenza virus infections. Proc Natl Acad Sci U S A 116, 4200-4205, doi:10.1073/pnas.1819197116 (2019). 27 Chen, J. R., Ma, C. Wong, C. H. Vaccine design of hemagglutinin glycoprotein against influenza. Trends Biotechnol 29, 426-434, doi:10.1016/j.tibtech.2011.04.007 (2011). 28 Chen, J.-R. et al. Vaccination of monoglycosylated hemagglutinin induces cross-strain protection against influenza virus infections. Proceedings of the National Academy of Sciences 111, 2476, doi:10.1073/pnas.1323954111 (2014). 29 Watanabe, Y. et al. Vulnerabilities in coronavirus glycan shields despite extensive glycosylation. bioRxiv, 2020.2002.2020.957472, doi:10.1101/2020.02.20.957472 (2020). 30 Grant, O. C., Montgomery, D., Ito, K. Woods, R. J. Analysis of the SARS-CoV-2 spike protein glycan shield reveals implications for immune recognition. Scientific Reports 10, 14991, doi:10.1038/s41598-020-71748-7 (2020). 31 Chen, J.-R. et al. Vaccination of monoglycosylated hemagglutinin induces cross-strain protection against influenza virus infections. Proceedings of the National Academy of Sciences 111, 2476-2481, doi:10.1073/pnas.1323954111 (2014). 32 Park, S.-J. et al. CHARMM-GUIGlycan Modelerfor modeling and simulation of carbohydrates and glycoconjugates. Glycobiology 29, 320-331, doi:10.1093/glycob/cwz003 (2019). 33 Eastman, P. et al. OpenMM 7: Rapid development of high performance algorithms for molecular dynamics. PLOS Computational Biology 13, e1005659, doi:10.1371/journal.pcbi.1005659 (2017). 34 Muñoz-Fontela, C. et al. Animal models for COVID-19. Nature 586, 509-515, doi:10.1038/s41586-020-2787-6 (2020). 35 Tsai, C.-Y. et al. Sex-biased response to and brain cell infection by SARS-CoV-2 in a highly susceptible human ACE2 transgenic model. bioRxiv, 2021.2005.2004.441029, doi:10.1101/2021.05.04.441029 (2021). 36 Liao, H.-Y. et al. Impact of Glycosylation on SARS-CoV-2 Infection and Broadly Protective Vaccine Design. bioRxiv, 2021.2005.2025.445523, doi:10.1101/2021.05.25.445523 (2021). 37 Callaway, E. The coronavirus is mutating - does it matter? Nature 585, 174-177, doi:10.1038/d41586-020-02544-6 (2020). 38 Vilar, S. Isom, D. G. One Year of SARS-CoV-2: How Much Has the Virus Changed? Biology 10, doi:10.3390/biology10020091 (2021). 39 Rausch, J. W., Capoferri, A. A., Katusiime, M. G., Patro, S. C. Kearney, M. F. Low genetic diversity may be an Achilles heel of SARS-CoV-2. Proceedings of the National Academy of Sciences 117, 24614, doi:10.1073/pnas.2017726117 (2020). 40 Wang, C.-C. et al. Glycans on influenza hemagglutinin affect receptor binding and immune response. Proceedings of the National Academy of Sciences of the United States of America 106, 18137-18142, doi:10.1073/pnas.0909696106 (2009). 41 Watanabe, Y., Allen, J. D., Wrapp, D., McLellan, J. S. Crispin, M. Site-specific glycan analysis of the SARS-CoV-2 spike. Science (New York, N.Y.) 369, 330-333, doi:10.1126/science.abb9983 (2020). 42 Sanchez-Felipe, L. et al. A single-dose live-attenuated YF17D-vectored SARS-CoV-2 vaccine candidate. Nature 590, 320-325, doi:10.1038/s41586-020-3035-9 (2021).
dc.identifier.urihttp://tdr.lib.ntu.edu.tw/jspui/handle/123456789/80969-
dc.description.abstract新冠肺炎 (COVID-19) 大流行促使了數百種針對新冠病毒 (SARS-CoV-2) 疫苗的開發。然而,儘管許多世衛組織批准的疫苗已顯示出很高的效力,但最近出現的許多變異株(variant) 造成的疫苗保護力下降進而引起了極大關注。此前,本實驗室所研發之單醣流感血凝素 (HAmg) 疫苗利用去除抗原中的聚醣屏蔽區,暴露了在原始全醣基化中難以接近且不易變異的抗原區域,因而展現較佳的跨病毒株保護力並誘導更好的免疫反應。憑藉流感研究的經驗,本研究研發出重組單醣棘蛋白 (Smg) 作為新冠肺炎疫苗,並分析其特性和免疫原性。疫苗開發主要目標的新冠病毒棘蛋白是一種高度醣化的病毒表面蛋白,在去除聚醣屏蔽後,Smg 可以激發更多針對病毒變異株之間不易變異抗原位的抗體。我們在小鼠、倉鼠和人類血管收縮素轉化酶2 (hACE2) 基因轉殖小鼠中進行疫苗接種實驗,並用酵素免疫分析法 (ELISA) 分析棘蛋白與抗體結合能力、免疫血清的中和效力以及病毒感染的保護作用時,發現 Smg 可以引發針對新冠病毒變異株更好的免疫反應,並有很大潛力成為對抗新冠肺炎更強大的武器。zh_TW
dc.description.provenanceMade available in DSpace on 2022-11-24T03:24:08Z (GMT). No. of bitstreams: 1
U0001-0709202114033100.pdf: 1716763 bytes, checksum: 73c3440fdfdbb82dbc589611cf8e0a58 (MD5)
Previous issue date: 2021
en
dc.description.tableofcontents口試委員會審定書 2 致謝 3 中文摘要 4 英文摘要 5 圖目錄: 6 Background 7 Learning achievement 9 Study 1: Development of glycoengineered Monoglycosylated Spike (Smg) protein vaccine 9 Study 2: Smg vaccination protects hamster and CAG-hACE2 transgenic mice from SARS-CoV-2 induced lung pathology 12 Study 3: The binding and neutralization ability against SARS-CoV-2 variants provided by Smg vaccine induced antibodies in mice 16 Conclusion and a way forward 19 Method and material: 20 References 27
dc.language.isoen
dc.subject新冠病毒棘蛋白zh_TW
dc.subject新冠肺炎zh_TW
dc.subject疫苗zh_TW
dc.subject變異株zh_TW
dc.subjectvariantsen
dc.subjectSARS-CoV-2 spikeen
dc.subjectCOVID-19en
dc.subjectvaccineen
dc.title單醣棘蛋白疫苗對SARS-CoV-2病毒及其變異株之保護力研究zh_TW
dc.titleMonoglycosylated Spike Vaccine Provides Better Protection against SARS-CoV-2 and its variantsen
dc.date.schoolyear109-2
dc.description.degree碩士
dc.contributor.coadvisor馬徹(Che Alex Ma)
dc.contributor.oralexamcommittee李財坤(Hsin-Tsai Liu),(Chih-Yang Tseng)
dc.subject.keyword新冠肺炎,疫苗,變異株,新冠病毒棘蛋白,zh_TW
dc.subject.keywordCOVID-19,vaccine,variants,SARS-CoV-2 spike,en
dc.relation.page30
dc.identifier.doi10.6342/NTU202103030
dc.rights.note同意授權(限校園內公開)
dc.date.accepted2021-09-09
dc.contributor.author-college醫學院zh_TW
dc.contributor.author-dept國際三校農業生技與健康醫療碩士學位學程zh_TW
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