請用此 Handle URI 來引用此文件：
http://tdr.lib.ntu.edu.tw/jspui/handle/123456789/95110完整後設資料紀錄
| DC 欄位 | 值 | 語言 |
|---|---|---|
| dc.contributor.advisor | 陶秘華 | zh_TW |
| dc.contributor.advisor | Mi-Hua Tao | en |
| dc.contributor.author | 邱千玲 | zh_TW |
| dc.contributor.author | Evelyn Eldora | en |
| dc.date.accessioned | 2024-08-28T16:18:55Z | - |
| dc.date.available | 2024-08-29 | - |
| dc.date.copyright | 2024-08-28 | - |
| dc.date.issued | 2024 | - |
| dc.date.submitted | 2024-08-08 | - |
| dc.identifier.citation | Naqvi, A.A.T., et al., Insights into SARS-CoV-2 genome, structure, evolution, pathogenesis and therapies: Structural genomics approach. Biochimica et Biophysica Acta (BBA) - Molecular Basis of Disease, 2020. 1866(10): p. 165878.
2. Enjuanes, L., et al., Nature of viruses and pandemics: Coronaviruses. Current Research in Immunology, 2022. 3: p. 151-158. 3. Cui, J., F. Li, and Z.-L. Shi, Origin and evolution of pathogenic coronaviruses. Nature Reviews Microbiology, 2019. 17(3): p. 181-192. 4. Zhu, N., et al., A Novel Coronavirus from Patients with Pneumonia in China, 2019. New England Journal of Medicine, 2020. 382(8): p. 727-733. 5. Groupé, V., DEMONSTRATION OF AN INTERFERENCE PHENOMENON ASSOCIATED WITH INFECTIOUS BRONCHITIS VIRUS (IBV) OF CHICKENS. Journal of Bacteriology, 1949. 58(1): p. 23-32. 6. Kapikian, A., The coronaviruses. Developments in Biological Standardization, 1975. 28: p. 42-64. 7. Su, S., et al., Epidemiology, Genetic Recombination, and Pathogenesis of Coronaviruses. Trends in Microbiology, 2016. 24(6): p. 490-502. 8. Chen, B., et al., Overview of lethal human coronaviruses. Signal Transduction and Targeted Therapy, 2020. 5(1). 9. Shi, Z., Emerging infectious diseases associated with bat viruses. Science China Life Sciences, 2013. 56(8): p. 678-682. 10. Frutos, R., et al., Emergence of Bat-Related Betacoronaviruses: Hazard and Risks. Frontiers in Microbiology, 2021. 12. 11. Bolles, M., E. Donaldson, and R. Baric, SARS-CoV and emergent coronaviruses: viral determinants of interspecies transmission. Current Opinion in Virology, 2011. 1(6): p. 624-634. 12. Corman, V.M., et al., Evidence for an Ancestral Association of Human Coronavirus 229E with Bats. Journal of Virology, 2015. 89(23): p. 11858-11870. 13. Hu, B., et al., Bat origin of human coronaviruses. Virology Journal, 2015. 12(1). 14. Huynh, J., et al., Evidence Supporting a Zoonotic Origin of Human Coronavirus Strain NL63. Journal of Virology, 2012. 86(23): p. 12816-12825. 15. Forni, D., et al., Molecular Evolution of Human Coronavirus Genomes. Trends in Microbiology, 2017. 25(1): p. 35-48. 16. Drexler, J.F., V.M. Corman, and C. Drosten, Ecology, evolution and classification of bat coronaviruses in the aftermath of SARS. Antiviral Research, 2014. 101: p. 45-56. 17. Ruiz-Aravena, M., et al., Ecology, evolution and spillover of coronaviruses from bats. Nature Reviews Microbiology, 2022. 20(5): p. 299-314. 18. Lau, S.K.P., et al., Molecular Evolution of Human Coronavirus 229E in Hong Kong and a Fatal COVID-19 Case Involving Coinfection with a Novel Human Coronavirus 229E Genogroup. mSphere, 2021. 6(1). 19. Lau, S.K.P., et al., Severe acute respiratory syndrome coronavirus-like virus in Chinese horseshoe bats. Proceedings of the National Academy of Sciences, 2005. 102(39): p. 14040-14045. 20. Zhou, P., et al., A pneumonia outbreak associated with a new coronavirus of probable bat origin. Nature, 2020. 579(7798): p. 270-273. 21. Lam, T.T.-Y., et al., Identifying SARS-CoV-2-related coronaviruses in Malayan pangolins. Nature, 2020. 583(7815): p. 282-285. 22. Baranowski, E., C.M. Ruiz-Jarabo, and E. Domingo, Evolution of Cell Recognition by Viruses. Science, 2001. 292(5519): p. 1102-1105. 23. Gallagher, T.M. and M.J. Buchmeier, Coronavirus Spike Proteins in Viral Entry and Pathogenesis. Virology, 2001. 279(2): p. 371-374. 24. Li, F., et al., Conformational States of the Severe Acute Respiratory Syndrome Coronavirus Spike Protein Ectodomain. Journal of Virology, 2006. 80(14): p. 6794-6800. 25. Li, F., Evidence for a Common Evolutionary Origin of Coronavirus Spike Protein Receptor-Binding Subunits. Journal of Virology, 2012. 86(5): p. 2856-2858. 26. Breslin, J.J., et al., Human Coronavirus 229E: Receptor Binding Domain and Neutralization by Soluble Receptor at 37°C. Journal of Virology, 2003. 77(7): p. 4435-4438. 27. Hofmann, H., et al., Highly Conserved Regions within the Spike Proteins of Human Coronaviruses 229E and NL63 Determine Recognition of Their Respective Cellular Receptors. Journal of Virology, 2006. 80(17): p. 8639-8652. 28. Kubo, H., Y.K. Yamada, and F. Taguchi, Localization of neutralizing epitopes and the receptor-binding site within the amino-terminal 330 amino acids of the murine coronavirus spike protein. Journal of Virology, 1994. 68(9): p. 5403-5410. 29. Lin, H.-X., et al., Identification of residues in the receptor-binding domain (RBD) of the spike protein of human coronavirus NL63 that are critical for the RBD–ACE2 receptor interaction. Journal of General Virology, 2008. 89(4): p. 1015-1024. 30. Graham, R.L. and R.S. Baric, Recombination, Reservoirs, and the Modular Spike: Mechanisms of Coronavirus Cross-Species Transmission. Journal of Virology, 2010. 84(7): p. 3134-3146. 31. Kuo, L., et al., Retargeting of Coronavirus by Substitution of the Spike Glycoprotein Ectodomain: Crossing the Host Cell Species Barrier. Journal of Virology, 2000. 74(3): p. 1393-1406. 32. Millet, J.K., J.A. Jaimes, and G.R. Whittaker, Molecular diversity of coronavirus host cell entry receptors. FEMS Microbiology Reviews, 2021. 45(3). 33. Hofmann, H., et al., Human coronavirus NL63 employs the severe acute respiratory syndrome coronavirus receptor for cellular entry. Proceedings of the National Academy of Sciences, 2005. 102(22): p. 7988-7993. 34. Li, W., et al., Angiotensin-converting enzyme 2 is a functional receptor for the SARS coronavirus. Nature, 2003. 426(6965): p. 450-454. 35. Wu, K., et al., Crystal structure of NL63 respiratory coronavirus receptor-binding domain complexed with its human receptor. Proceedings of the National Academy of Sciences, 2009. 106(47): p. 19970-19974. 36. Raj, V.S., et al., Dipeptidyl peptidase 4 is a functional receptor for the emerging human coronavirus-EMC. Nature, 2013. 495(7440): p. 251-254. 37. Starr, T.N., et al., ACE2 binding is an ancestral and evolvable trait of sarbecoviruses. Nature, 2022. 603(7903): p. 913-918. 38. Wells, H.L., et al., The evolutionary history of ACE2 usage within the coronavirus subgenus <i>Sarbecovirus</i>. Virus Evolution, 2021. 7(1). 39. Ge, X.-Y., et al., Isolation and characterization of a bat SARS-like coronavirus that uses the ACE2 receptor. Nature, 2013. 503(7477): p. 535-538. 40. Hu, B., et al., Discovery of a rich gene pool of bat SARS-related coronaviruses provides new insights into the origin of SARS coronavirus. PLOS Pathogens, 2017. 13(11): p. e1006698. 41. Li, W., et al., Bats Are Natural Reservoirs of SARS-Like Coronaviruses. Science, 2005. 310(5748): p. 676-679. 42. Ren, W., et al., Difference in Receptor Usage between Severe Acute Respiratory Syndrome (SARS) Coronavirus and SARS-Like Coronavirus of Bat Origin. Journal of Virology, 2008. 82(4): p. 1899-1907. 43. Yang, X.-L., et al., Isolation and Characterization of a Novel Bat Coronavirus Closely Related to the Direct Progenitor of Severe Acute Respiratory Syndrome Coronavirus. Journal of Virology, 2016. 90(6): p. 3253-3256. 44. Letko, M., A. Marzi, and V. Munster, Functional assessment of cell entry and receptor usage for SARS-CoV-2 and other lineage B betacoronaviruses. Nature Microbiology, 2020. 5(4): p. 562-569. 45. Si, J., et al., Sarbecovirus RBD indels and specific residues dictating ACE2 multi-species adaptiveness. 2024, Cold Spring Harbor Laboratory. 46. Lindstrom, S.E., N.J. Cox, and A. Klimov, Genetic analysis of human H2N2 and early H3N2 influenza viruses, 1957–1972: evidence for genetic divergence and multiple reassortment events. Virology, 2004. 328(1): p. 101-119. 47. Xu, X., et al., Reassortment and evolution of current human influenza A and B viruses. Virus Research, 2004. 103(1-2): p. 55-60. 48. Oprisan, G., et al., Natural genetic recombination between co-circulating heterotypic enteroviruses. Journal of General Virology, 2002. 83(9): p. 2193-2200. 49. Huang, T., et al., Evidence of Recombination and Genetic Diversity in Human Rhinoviruses in Children with Acute Respiratory Infection. PLoS ONE, 2009. 4(7): p. e6355. 50. Singh, D. and S.V. Yi, On the origin and evolution of SARS-CoV-2. Experimental & Molecular Medicine, 2021. 53(4): p. 537-547. 51. Payne, S., Virus evolution and genetics. 2023, Elsevier. p. 107-118. 52. Lai, M.M., et al., Recombination between nonsegmented RNA genomes of murine coronaviruses. Journal of Virology, 1985. 56(2): p. 449-456. 53. Tian, P.-F., et al., Evidence of Recombinant Strains of Porcine Epidemic Diarrhea Virus, United States, 2013. Emerging Infectious Diseases, 2014. 20(10): p. 1731-1734. 54. Decaro, N., et al., Recombinant Canine Coronaviruses Related to Transmissible Gastroenteritis Virus of Swine Are Circulating in Dogs. Journal of Virology, 2009. 83(3): p. 1532-1537. 55. Herrewegh, A.A.P.M., et al., Feline Coronavirus Type II Strains 79-1683 and 79-1146 Originate from a Double Recombination between Feline Coronavirus Type I and Canine Coronavirus. Journal of Virology, 1998. 72(5): p. 4508-4514. 56. Kin, N., et al., Genomic Analysis of 15 Human Coronaviruses OC43 (HCoV-OC43s) Circulating in France from 2001 to 2013 Reveals a High Intra-Specific Diversity with New Recombinant Genotypes. Viruses, 2015. 7(5): p. 2358-2377. 57. Lau, S.K.P., et al., Molecular Epidemiology of Human Coronavirus OC43 Reveals Evolution of Different Genotypes over Time and Recent Emergence of a Novel Genotype due to Natural Recombination. Journal of Virology, 2011. 85(21): p. 11325-11337. 58. Zhang, Y., et al., Genotype shift in human coronavirus OC43 and emergence of a novel genotype by natural recombination. Journal of Infection, 2015. 70(6): p. 641-650. 59. Pyrc, K., et al., Mosaic Structure of Human Coronavirus NL63, One Thousand Years of Evolution. Journal of Molecular Biology, 2006. 364(5): p. 964-973. 60. Woo, P.C.Y., et al., Phylogenetic and recombination analysis of coronavirus HKU1, a novel coronavirus from patients with pneumonia. Archives of Virology, 2005. 150(11): p. 2299-2311. 61. Woo, P.C.Y., et al., Comparative Analysis of 22 Coronavirus HKU1 Genomes Reveals a Novel Genotype and Evidence of Natural Recombination in Coronavirus HKU1. Journal of Virology, 2006. 80(14): p. 7136-7145. 62. Stanhope, M.J., J.R. Brown, and H. Amrine-Madsen, Evidence from the evolutionary analysis of nucleotide sequences for a recombinant history of SARS-CoV. Infection, Genetics and Evolution, 2004. 4(1): p. 15-19. 63. Sabir, J.S.M., et al., Co-circulation of three camel coronavirus species and recombination of MERS-CoVs in Saudi Arabia. Science, 2016. 351(6268): p. 81-84. 64. Tao, Y., et al., Surveillance of Bat Coronaviruses in Kenya Identifies Relatives of Human Coronaviruses NL63 and 229E and Their Recombination History. Journal of Virology, 2017. 91(5): p. JVI.01953-16. 65. Licitra, B., G. Duhamel, and G. Whittaker, Canine Enteric Coronaviruses: Emerging Viral Pathogens with Distinct Recombinant Spike Proteins. Viruses, 2014. 6(8): p. 3363-3376. 66. Regan, A.D., et al., Characterization of a recombinant canine coronavirus with a distinct receptor-binding (S1) domain. Virology, 2012. 430(2): p. 90-99. 67. Wu, F., et al., A new coronavirus associated with human respiratory disease in China. Nature, 2020. 579(7798): p. 265-269. 68. Gorbalenya, A.E., et al., The species Severe acute respiratory syndrome-related coronavirus: classifying 2019-nCoV and naming it SARS-CoV-2. Nature Microbiology, 2020. 5(4): p. 536-544. 69. Markov, P.V., et al., The evolution of SARS-CoV-2. Nature Reviews Microbiology, 2023. 21(6): p. 361-379. 70. Shrestha, L.B., et al., Evolution of the SARS‐CoV‐2 omicron variants BA. 1 to BA. 5: implications for immune escape and transmission. Reviews in Medical Virology, 2022. 32(5): p. e2381. 71. Tegally, H., et al., Emergence of SARS-CoV-2 Omicron lineages BA.4 and BA.5 in South Africa. Nature Medicine, 2022. 28(9): p. 1785-1790. 72. Pipek, O.A., et al., Systematic detection of co-infection and intra-host recombination in more than 2 million global SARS-CoV-2 samples. Nature Communications, 2024. 15(1). 73. Mohapatra, R.K., et al., The recombinant variants of SARS‐CoV‐2: Concerns continues amid COVID‐19 pandemic. Journal of Medical Virology, 2022. 94(8): p. 3506-3508. 74. Tamura, T., et al., Virological characteristics of the SARS-CoV-2 XBB variant derived from recombination of two Omicron subvariants. Nature Communications, 2023. 14(1). 75. Breman, J.G., Smallpox. The Journal of Infectious Diseases, 2021. 224(Supplement_4): p. S379-S386. 76. Nagy, A. and B. Alhatlani, An overview of current COVID-19 vaccine platforms. Computational and Structural Biotechnology Journal, 2021. 19: p. 2508-2517. 77. Krammer, F., SARS-CoV-2 vaccines in development. Nature, 2020. 586(7830): p. 516-527. 78. Li, M., et al., COVID-19 vaccine development: milestones, lessons and prospects. Signal Transduction and Targeted Therapy, 2022. 7(1). 79. Hossain, M.K., et al., The race for a COVID-19 vaccine: where are we up to? Expert Review of Vaccines, 2022. 21(3): p. 355-376. 80. Hu, L., et al., A Review of Inactivated COVID-19 Vaccine Development in China: Focusing on Safety and Efficacy in Special Populations. Vaccines, 2023. 11(6): p. 1045. 81. Yadav, P.D., et al., Immunogenicity and protective efficacy of inactivated SARS-CoV-2 vaccine candidate, BBV152 in rhesus macaques. Nature Communications, 2021. 12(1). 82. Tanriover, M.D., et al., Efficacy and safety of an inactivated whole-virion SARS-CoV-2 vaccine (CoronaVac): interim results of a double-blind, randomised, placebo-controlled, phase 3 trial in Turkey. The Lancet, 2021. 398(10296): p. 213-222. 83. WHO. Evidence Assessment: Sinopharm/BBIBP COVID-19 Vaccine. 2021 [cited 2024 July 10]; Available from: https://cdn.who.int/media/docs/default-source/immunization/sage/2021/april/2_sage29apr2021_critical-evidence_sinopharm.pdf. 84. Ella, R., et al., Efficacy, safety, and lot-to-lot immunogenicity of an inactivated SARS-CoV-2 vaccine (BBV152): interim results of a randomised, double-blind, controlled, phase 3 trial. The Lancet, 2021. 398(10317): p. 2173-2184. 85. Barchuk, A., et al., Gam-COVID-Vac, EpiVacCorona, and CoviVac effectiveness against lung injury during Delta and Omicron variant surges in St. Petersburg, Russia: a test-negative case–control study. Respiratory Research, 2022. 23(1). 86. Heath, P.T., et al., Safety and Efficacy of NVX-CoV2373 Covid-19 Vaccine. New England Journal of Medicine, 2021. 385(13): p. 1172-1183. 87. Dai, L., et al., Efficacy and Safety of the RBD-Dimer–Based Covid-19 Vaccine ZF2001 in Adults. New England Journal of Medicine, 2022. 386(22): p. 2097-2111. 88. Ura, T., K. Okuda, and M. Shimada, Developments in Viral Vector-Based Vaccines. Vaccines, 2014. 2(3): p. 624-641. 89. Knoll, M.D. and C. Wonodi, Oxford–AstraZeneca COVID-19 vaccine efficacy. The Lancet, 2021. 397(10269): p. 72-74. 90. Sadoff, J., et al., Safety and Efficacy of Single-Dose Ad26.COV2.S Vaccine against Covid-19. New England Journal of Medicine, 2021. 384(23): p. 2187-2201. 91. WHO. The CanSino Biologics Ad5-nCoV-S [recombinant] COVID-19 vaccine: What you need to know. 2022 [cited 2024 July 10]; Available from: https://www.who.int/news-room/feature-stories/detail/the--cansino-biologics-ad5-ncov-s--recombinant---covid-19-vaccine--what-you-need-to-know. 92. Logunov, D.Y., et al., Safety and immunogenicity of an rAd26 and rAd5 vector-based heterologous prime-boost COVID-19 vaccine in two formulations: two open, non-randomised phase 1/2 studies from Russia. The Lancet, 2020. 396(10255): p. 887-897. 93. Polack, F.P., et al., Safety and Efficacy of the BNT162b2 mRNA Covid-19 Vaccine. New England Journal of Medicine, 2020. 383(27): p. 2603-2615. 94. Baden, L.R., et al., Efficacy and Safety of the mRNA-1273 SARS-CoV-2 Vaccine. New England Journal of Medicine, 2021. 384(5): p. 403-416. 95. Zhou, D., et al., Evidence of escape of SARS-CoV-2 variant B.1.351 from natural and vaccine-induced sera. Cell, 2021. 184(9): p. 2348-2361.e6. 96. Wall, E.C., et al., Neutralising antibody activity against SARS-CoV-2 VOCs B.1.617.2 and B.1.351 by BNT162b2 vaccination. The Lancet, 2021. 397(10292): p. 2331-2333. 97. Cao, Y., et al., Omicron escapes the majority of existing SARS-CoV-2 neutralizing antibodies. Nature, 2022. 602(7898): p. 657-663. 98. Planas, D., et al., Considerable escape of SARS-CoV-2 Omicron to antibody neutralization. Nature, 2022. 602(7898): p. 671-675. 99. Kurhade, C., et al., Low neutralization of SARS-CoV-2 Omicron BA.2.75.2, BQ.1.1 and XBB.1 by parental mRNA vaccine or a BA.5 bivalent booster. Nature Medicine, 2023. 29(2): p. 344-347. 100. Ma, K.C., et al., Effectiveness of Updated 2023–2024 (Monovalent XBB.1.5) COVID-19 Vaccination Against SARS-CoV-2 Omicron XBB and BA.2.86/JN.1 Lineage Hospitalization and a Comparison of Clinical Severity — IVY Network, 26 Hospitals, October 18, 2023–March 9, 2024. 2024, Cold Spring Harbor Laboratory. 101. Middleton, D., et al., Hendra Virus Vaccine, a One Health Approach to Protecting Horse, Human, and Environmental Health. Emerging Infectious Diseases, 2014. 20(3). 102. Cohen, A.A., et al., Mosaic nanoparticles elicit cross-reactive immune responses to zoonotic coronaviruses in mice. Science, 2021. 371(6530): p. 735-741. 103. Cohen, A.A., et al., Mosaic RBD nanoparticles protect against challenge by diverse sarbecoviruses in animal models. Science, 2022. 377(6606). 104. Walls, A.C., et al., Elicitation of Potent Neutralizing Antibody Responses by Designed Protein Nanoparticle Vaccines for SARS-CoV-2. Cell, 2020. 183(5): p. 1367-1382.e17. 105. Feng, Y., et al., Broadly neutralizing antibodies against sarbecoviruses generated by immunization of macaques with an AS03-adjuvanted COVID-19 vaccine. Science Translational Medicine, 2023. 15(695). 106. Walls, A.C., et al., Elicitation of broadly protective sarbecovirus immunity by receptor-binding domain nanoparticle vaccines. Cell, 2021. 184(21): p. 5432-5447.e16. 107. Wu, Y., et al., Lineage-mosaic and mutation-patched spike proteins for broad-spectrum COVID-19 vaccine. Cell Host & Microbe, 2022. 30(12): p. 1732-1744.e7. 108. Hu, Q., et al., Chimeric mRNA-based COVID-19 vaccine induces protective immunity against Omicron and Delta variants. Molecular Therapy - Nucleic Acids, 2022. 30: p. 465-476. 109. Martinez, D.R., et al., Chimeric spike mRNA vaccines protect against Sarbecovirus challenge in mice. Science, 2021. 373(6558): p. 991-998. 110. Patiño-Galindo, J.Á., et al., Recombination and lineage-specific mutations linked to the emergence of SARS-CoV-2. Genome Medicine, 2021. 13(1). 111. Delaye, L. and L. Román-Padilla, Untangling the Evolution of the Receptor-Binding Motif of SARS-CoV-2. Journal of Molecular Evolution, 2024. 92(3): p. 329-337. 112. Dong, Y., et al., A systematic review of SARS-CoV-2 vaccine candidates. Signal Transduction and Targeted Therapy, 2020. 5(1). 113. Liu, L., et al., Potent neutralizing antibodies against multiple epitopes on SARS-CoV-2 spike. Nature, 2020. 584(7821): p. 450-456. 114. Lee, W.S., et al., Antibody-dependent enhancement and SARS-CoV-2 vaccines and therapies. Nature Microbiology, 2020. 5(10): p. 1185-1191. 115. Katzelnick, L.C., et al., Antibody-dependent enhancement of severe dengue disease in humans. Science, 2017. 358(6365): p. 929-932. 116. Winarski, K.L., et al., Antibody-dependent enhancement of influenza disease promoted by increase in hemagglutinin stem flexibility and virus fusion kinetics. Proceedings of the National Academy of Sciences, 2019. 116(30): p. 15194-15199. 117. Iankov, I.D., et al., Immunoglobulin G Antibody-Mediated Enhancement of Measles Virus Infection Can Bypass the Protective Antiviral Immune Response. Journal of Virology, 2006. 80(17): p. 8530-8540. 118. Agrawal, A.S., et al., Immunization with inactivated Middle East Respiratory Syndrome coronavirus vaccine leads to lung immunopathology on challenge with live virus. Human Vaccines & Immunotherapeutics, 2016. 12(9): p. 2351-2356. 119. Jaume, M., et al., Anti-Severe Acute Respiratory Syndrome Coronavirus Spike Antibodies Trigger Infection of Human Immune Cells via a pH- and Cysteine Protease-Independent FcγR Pathway. Journal of Virology, 2011. 85(20): p. 10582-10597. 120. Okuya, K., et al., Multiple Routes of Antibody-Dependent Enhancement of SARS-CoV-2 Infection. Microbiology Spectrum, 2022. 10(2). 121. Andrade, V.M., et al., Delineation of DNA and mRNA COVID-19 vaccine-induced immune responses in preclinical animal models. Human Vaccines & Immunotherapeutics, 2023. 19(3). 122. Wang, H., et al., Recombination in Positive-Strand RNA Viruses. Front Microbiol, 2022. 13: p. 870759. 123. Singh, P., et al., Mosaic Recombination Inflicted Various SARS-CoV-2 Lineages to Emerge into Novel Virus Variants: a Review Update. Indian Journal of Clinical Biochemistry, 2023. 38(4): p. 418-425. | - |
| dc.identifier.uri | http://tdr.lib.ntu.edu.tw/jspui/handle/123456789/95110 | - |
| dc.description.abstract | 新冠肺炎自2019年大爆發以來，病毒持續變異，儘管臨床上已有許多疫苗及藥物來預防及治療，其傳播力及免疫逃脫能力都持續增強，至今仍是全球健康體系的一大挑戰。胺基酸變異和重組造成的冠狀病毒多樣性降低了疫苗的預防效果，尤其是近來的新冠狀病毒重組變異體XBB。XBB病毒是BJ.1 and BM.1.1.1重組產生的，在刺突蛋白的受體結合結構域（RBD）中發生了重組。這種變異具有免疫逃脫及傳播性增加的特性。因此，我們需要開發新型疫苗能對各種新冠狀病毒變種和未來的Sarbecovirus具有廣泛的保護力。本研究想要透過從五種Sarbecovirus（SARS-CoV、 Delta、Omicron BA.2、穿山甲和蝙蝠冠狀病毒）中建立嵌合受體結合結構域（RBD）庫來開發對Sarbecovirus的廣效疫苗。利用PCR的片段擴增以及Golden Gate組裝，此文庫理論上有3125個獨特的嵌合RBD變異體。這個策略能反映自然界觀察到的冠狀病毒重組事件。到目前為止，已經鑑定出757種獨特的嵌合RBD，而它們均對與人類血管緊張素轉換酶2（hACE2）受體表現出不同的親和力。在建構文庫後，透過流式細胞儀的初步體外篩選，嚴格篩選出134個能對於hACE2具有很強親和力的嵌合RBD候選物，為“嵌合RBD疫苗”。這些嵌合RBD疫苗進一步在小鼠體內進行了免疫試驗。以87種嵌合RBD疫苗免疫的初步篩選結果表明， 26種疫苗對BA.4/5假病毒表現出交叉反應。尤其這些疫苗缺乏BA.4/5 RBD序列，MU4、XE3、WZ3和FC4仍然可以產生交叉反應高於Delta疫苗。特別是，與親代疫苗相比，XE3疫苗針對Omicron BA.4/5變異株引發了顯著更高的中和抗體水平。這結果表示XE3對多種Sarbecovirus變體具有潛在的廣效保護能力。總之，本研究為開發具有廣效保護能力的下一代新冠肺炎疫苗提供了策略。血清庫和疫苗庫篩選策略能幫忙加速未來疫苗開發工作。我們的策略強調了嵌合RBD疫苗在廣效保護以及增強對不斷發展的Sarbecovirus變異株的效率方面的潛力，有助於為未來的流行病做好準備。 | zh_TW |
| dc.description.abstract | The COVID-19 outbreak, caused by SARS-CoV-2, emerged in 2019 and rapidly escalated into a global pandemic. Despite the development of numerous clinical vaccines and therapeutic drugs, the persistent evolution of the virus continues to pose significant challenges. The virus's ability to mutate enhances its transmissibility and enables immune evasion, maintaining COVID-19 as a critical global health issue. The diversity of coronaviruses, driven by amino acid variations and recombination events, undermines the effectiveness of existing vaccines, especially the recent new recombinant variant XBB. XBB variant, a recombinant of two BA.2 lineages (BJ.1 and BM.1.1.1), has a recombination breakpoint in the spike protein's receptor-binding domain (RBD). This variant has acquired characteristics such as increased immune evasion and transmissibility, raising concerns about the adaptability of current vaccines. As a result, there is an urgent need for novel vaccines with broad protection against diverse SARS-CoV-2 variants and future Sarbecoviruses. This study aimed to develop a pan-Sarbecovirus vaccine strategy by creating a chimeric receptor binding domain (RBD) library from five Sarbecoviruses: SARS-CoV, Delta, Omicron BA.2, Pangolin coronavirus, and bat coronavirus. Using PCR-based fragment amplification and golden-gate assembly, the generated library theoretically consists of 3125 unique chimeric RBD variants, reflecting natural recombination events observed in coronavirus. So far, 757 unique chimeric RBDs have been identified, each demonstrating distinct binding affinities for the human angiotensin-converting enzyme 2 (hACE2) receptor. Following library construction, rigorous screening identified 134 chimeric RBD candidates with very strong hACE2 binding affinities through initial in vitro evaluations using flow cytometry. These selected candidates, termed "chimeric RBD vaccines," underwent in vivo immunization trials in mice. Preliminary results from immunization with 87 chimeric RBD vaccines indicated that 26 exhibited cross-neutralization capabilities against BA.4/5 pseudoviruses in collected mouse sera. Interestingly, vaccine candidates MU4, XE3, WZ3, and FC4 demonstrated higher pseudovirus inhibition percentages than the Delta vaccine, despite lacking BA.4/5 RBD sequences. In particular, the XE3 vaccine elicited significantly higher levels of neutralizing antibodies against the Omicron BA.4/5 sublineages when compared with parental vaccines, suggesting potential broad-spectrum protection against diverse Sarbecovirus variants. In conclusion, this study presents a strategy for developing next-generation COVID-19 vaccines with broad-spectrum protection capabilities. Serum bank establishment and versatile screening tools represent significant advancements that can expedite future vaccine development efforts. Our strategy highlights the potential of chimeric RBD vaccines for broad-spectrum protection and enhanced efficacy against emerging and evolving Sarbecovirus variants, contributing to preparedness for future pandemics. | en |
| dc.description.provenance | Submitted by admin ntu (admin@lib.ntu.edu.tw) on 2024-08-28T16:18:55Z No. of bitstreams: 0 | en |
| dc.description.provenance | Made available in DSpace on 2024-08-28T16:18:55Z (GMT). No. of bitstreams: 0 | en |
| dc.description.tableofcontents | 致謝 i
中文摘要 iii Abstract iv Table of contents vi List of figures ix Chapter 1 Introduction 1 1.1 Introduction to Coronaviruses 1 1.1.1 Overview of coronavirus 1 1.1.2 Coronavirus host origin 2 1.2 Host tropism in coronaviruses 3 1.2.1 Role of the receptor-binding domain of the spike gene 3 1.2.2 Evolvability of ACE2 binding 4 1.3 Recombination in coronavirus 5 1.3.1 Mechanism of coronaviruses recombination 5 1.3.2 Evidence of recombination in animal and human coronaviruses 6 1.4 SARS-CoV-2 evolution 6 1.4.1 SARS-CoV-2 Variants of Concern 7 1.4.2 Omicron and its subvariants 7 1.4.3 Recombination in SARS-CoV-2 variants 8 1.5 COVID-19 vaccine 8 1.5.1 Types of COVID-19 vaccines 9 1.5.2 Challenges of currently available COVID-19 vaccines 11 1.6 Strategy of broadly protective vaccines development 12 1.6.1 Nanoparticle vaccine 13 1.6.2 Chimeric antigen vaccine 14 1.7 Study design 15 Chapter 2 Materials and methods 16 2.1 Mice and ethics 16 2.2 Cell lines and viruses 16 2.3 RBD plasmid 16 2.4 Selection of recombination sites 17 2.5 Construction of expression vectors for RBD DNA vaccine 17 2.5.1 Site directed mutagenesis 18 2.5.2 p3224-3-IgK-eGFP-His expression plasmid construction 19 2.6 Parental RBD cloning 21 2.7 Chimeric RBD library construction 22 2.7.1 Preparation of RBD fragments 22 2.7.2 Golden Gate assembly for chimeric RBD assembly 23 2.8 Flow cytometry for RBD-hACE2 binding affinity assessment 24 2.9 Preparation of chimeric RBD DNA vaccine 24 2.10 Electroporation‐mediated DNA immunization into mice 25 2.11 Recombinant RBD protein production 25 2.11.1 Expression of RBD protein 25 2.11.2 RBD protein purification 26 2.11.3 BCA protein concentration assay 28 2.11.4 SDS-PAGE analysis 28 2.12 ELISA binding assay 28 2.13 SARS-CoV-2 variants pseudovirus neutralization assay 29 2.14 Serum bank collection and management 29 2.15 Statistical analysis 30 Chapter 3 Results 31 3.1 Selection of Sarbecovirus parental strains for chimeric RBD vaccine 31 3.2 Assigning four recombination breakpoint sites across RBD region 31 3.3 Generation of chimeric RBD library using Golden Gate cloning 33 3.4 757 of total 3120 unique chimeric RBDs have been found 34 3.5 Chimeric RBD library screening strategy 35 3.6 Binding characteristic of parental RBDs to hACE2 36 3.7 134 chimeric RBDs possess very strong binding affinity to hACE2 36 3.8 Immunogenicity of parental RBD vaccines in mice 37 3.9 Immunogenicity of chimeric RBD in mice 39 3.10 Chimeric RBD vaccines show cross-reactivity to SARS-CoV-2 variant 40 Chapter 4 Discussion 42 References 46 | - |
| dc.language.iso | en | - |
| dc.title | 嵌合RBD庫：一種嶄新的疫苗策略用於製造廣效冠狀病毒疫苗 | zh_TW |
| dc.title | Chimeric RBD Library: A Novel Strategy for Developing Broad-spectrum Sarbecovirus Vaccine | en |
| dc.type | Thesis | - |
| dc.date.schoolyear | 112-2 | - |
| dc.description.degree | 碩士 | - |
| dc.contributor.oralexamcommittee | 張淑媛;林靜宜;王宜萱 | zh_TW |
| dc.contributor.oralexamcommittee | Sui-Yuan Chang;Jing-Yi Lin;I-Hsuan Wang | en |
| dc.subject.keyword | 新型冠狀病毒,病毒重組,受體結合區,廣效疫苗,嵌合RBD疫苗,廣效性中和抗體,高關注變異株, | zh_TW |
| dc.subject.keyword | SARS-CoV-2,Sarbecovirus,recombinant virus,receptor-binding domain (RBD),universal vaccine,chimeric RBD vaccine,cross-neutralizing antibody response,variants of concern (VOC), | en |
| dc.relation.page | 103 | - |
| dc.identifier.doi | 10.6342/NTU202403828 | - |
| dc.rights.note | 同意授權(限校園內公開) | - |
| dc.date.accepted | 2024-08-08 | - |
| dc.contributor.author-college | 醫學院 | - |
| dc.contributor.author-dept | 醫學檢驗暨生物技術學系 | - |
| dc.date.embargo-lift | 2027-08-01 | - |
| 顯示於系所單位： | 醫學檢驗暨生物技術學系 | |
文件中的檔案：
| 檔案 | 大小 | 格式 | |
|---|---|---|---|
| ntu-112-2.pdf 目前未授權公開取用 | 14.51 MB | Adobe PDF | 檢視/開啟 |
系統中的文件，除了特別指名其著作權條款之外，均受到著作權保護，並且保留所有的權利。