Skip to main content
Wiley - PMC COVID-19 Collection logoLink to Wiley - PMC COVID-19 Collection
. 2006 Mar 3;16(2):117–131. doi: 10.1002/rmv.492

Severe acute respiratory syndrome (SARS) coronavirus: application of monoclonal antibodies and development of an effective vaccine

Yasuko Tsunetsugu‐Yokota 1, Kazuo Ohnishi 1, Toshitada Takemori 1,
PMCID: PMC7169118  PMID: 16518829

Abstract

SARS‐CoV is a new type of human coronavirus identified as a causative agent of severe acute respiratory syndrome (SARS). On the occasion of the SARS outbreak, various monoclonal antibodies (mAbs) against SARS‐CoV have been developed and applied for diagnosis, clinical management and basic research. In this review, we overview the biochemical and functional properties and applications of these SARS‐CoV mAbs. We also focus on a variety of vaccines currently under development and discuss the immune response elicited by these vaccines in animal models, hopefully to better understand what we need to do next to fight against newly emerging pathogens in the future. Copyright © 2006 John Wiley & Sons, Ltd.

REFERENCES

  • 1. Marra MA, Jones SJ, Astell CR, et al The genome sequence of the SARS‐associated coronavirus. Science 2003; 300: 1399–1404. [DOI] [PubMed] [Google Scholar]
  • 2. Rota PA, Oberste MS, Monroe SS, et al Characterization of a novel coronavirus associated with severe acute respiratory syndrome. Science 2003; 300: 1394–1399. [DOI] [PubMed] [Google Scholar]
  • 3. Peiris JS, Guan Y, Yuen KY. Severe acute respiratory syndrome. Nat Med 2004; 10: S88–97. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 4. Lau SK, Woo PC, Li KS, et al Severe acute respiratory syndrome coronavirus‐like virus in Chinese horseshoe bats. Proc Natl Acad Sci USA 2005; 102: 14040–14045. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 5. Li G, Chen X, Xu A. Profile of specific antibodies to the SARS‐associated coronavirus. N Engl J Med 2003; 349: 508–509. [DOI] [PubMed] [Google Scholar]
  • 6. Clarke T. SARS What have we learned? What about vaccine? Nature 2003; 424: 126. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 7. Subbarao K, McAuliffe J, Vogel L, et al Prior infection and passive transfer of neutralizing antibody prevent replication of severe acute respiratory syndrome coronavirus in the respiratory tract of mice. J Virol 2004; 78: 3572–3577. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 8. Li W, Moore MJ, Vasilieva N, et al Angiotensin‐converting enzyme 2 is a functional receptor for the SARS coronavirus. Nature 2003; 426: 450–454. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 9. Wong SK, Li W, Moore MJ, Choe H, Farzan M. A 193‐amino acid fragment of the SARS coronavirus S protein efficiently binds angiotensin‐converting enzyme 2. J Biol Chem 2004; 279: 3197–3201. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 10. Ohnishi K, Sakaguchi M, Kaji T, et al Immunological detection of severe acute respiratory syndrome coronavirus by monoclonal antibodies. Jpn J Infect Dis 2005; 58: 88–94. [PubMed] [Google Scholar]
  • 11. Chou TH, Wang S, Sakhatskyy PV, et al Epitope mapping and biological function analysis of antibodies produced by immunization of mice with an inactivated Chinese isolate of severe acute respiratory syndrome‐associated coronavirus (SARS‐CoV). Virology 2005; 334: 134–143. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 12. Gubbins MJ, Plummer FA, Yuan XY, et al Molecular characterization of a panel of murine monoclonal antibodies specific for the SARS‐coronavirus. Mol Immunol 2005; 42: 125–136. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 13. Zhou T, Wang H, Luo D, et al An exposed domain in the severe acute respiratory syndrome coronavirus spike protein induces neutralizing antibodies. J Virol 2004; 78: 7217–7226. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 14. He Y, Zhou Y, Liu S, et al Receptor‐binding domain of SARS‐CoV spike protein induces highly potent neutralizing antibodies: implication for developing subunit vaccine. Biochem Biophys Res Commun 2004; 324: 773–781. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 15. Che XY, Qiu LW, Pan YX, et al Sensitive and specific monoclonal antibody‐based capture enzyme immunoassay for detection of nucleocapsid antigen in sera from patients with severe acute respiratory syndrome. J Clin Microbiol 2004; 42: 2629–2635. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 16. Traggiai E, Becker S, Subbarao K, et al An efficient method to make human monoclonal antibodies from memory B cells: potent neutralization of SARS coronavirus. Nat Med 2004; 10: 871–875. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 17. Sui J, Li W, Murakami A, et al Potent neutralization of severe acute respiratory syndrome (SARS) coronavirus by a human mAb to S1 protein that blocks receptor association. Proc Natl Acad Sci USA 2004; 101: 2536–2541. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 18. van den Brink EN, Ter Meulen J, Cox F, et al Molecular and biological characterization of human monoclonal antibodies binding to the spike and nucleocapsid proteins of severe acute respiratory syndrome coronavirus. J Virol 2005; 79: 1635–1644. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 19. Duan J, Yan X, Guo X, et al A human SARS‐CoV neutralizing antibody against epitope on S2 protein. Biochem Biophys Res Commun 2005; 333: 186–193. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 20. Ishida I, Tomizuka K, Yoshida H, et al Production of human monoclonal and polyclonal antibodies in TransChromo animals. Cloning Stem Cells 2002; 4: 91–102. [DOI] [PubMed] [Google Scholar]
  • 21. Greenough TC, Babcock GJ, Roberts A, et al Development and characterization of a severe acute respiratory syndrome‐associated coronavirus‐neutralizing human monoclonal antibody that provides effective immunoprophylaxis in mice. J Infect Dis 2005; 191: 507–514. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 22. Buchholz UJ, Bukreyev A, Yang L, et al Contributions of the structural proteins of severe acute respiratory syndrome coronavirus to protective immunity. Proc Natl Acad Sci USA 2004; 101: 9804–9809. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 23. Guo JP, Petric M, Campbell W, McGeer PL. SARS corona virus peptides recognized by antibodies in the sera of convalescent cases. Virology 2004; 324: 251–256. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 24. Wang J, Wen J, Li J, et al Assessment of immunoreactive synthetic peptides from the structural proteins of severe acute respiratory syndrome coronavirus. Clin Chem 2003; 49: 1989–1996. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 25. Yeager CL, Ashmun RA, Williams RK, et al Human aminopeptidase N is a receptor for human coronavirus 229E. Nature 1992; 357: 420–422. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 26. Delmas B, Gelfi J, L'Haridon R, et al Aminopeptidase N is a major receptor for the entero‐pathogenic coronavirus TGEV. Nature 1992; 357: 417–420. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 27. Bonavia A, Zelus BD, Wentworth DE, Talbot PJ, Holmes KV. Identification of a receptor‐binding domain of the spike glycoprotein of human coronavirus HCoV‐229E. J Virol 2003; 77: 2530–2538. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 28. Godet M, Grosclaude J, Delmas B, Laude H. Major receptor‐binding and neutralization determinants are located within the same domain of the transmissible gastroenteritis virus (coronavirus) spike protein. J Virol 1994; 68: 8008–8016. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 29. Dveksler GS, Dieffenbach CW, Cardellichio CB, et al Several members of the mouse carcinoembryonic antigen‐related glycoprotein family are functional receptors for the coronavirus mouse hepatitis virus‐A59. J Virol 1993; 67: 1–8. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 30. Kubo H, Yamada YK, Taguchi F. Localization of neutralizing epitopes and the receptor‐binding site within the amino‐terminal 330 amino acids of the murine coronavirus spike protein. J Virol 1994; 68: 5403–5410. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 31. Matsuyama S, Taguchi F. Receptor‐induced conformational changes of murine coronavirus spike protein. J Virol 2002; 76: 11819–11826. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 32. Zelus BD, Schickli JH, Blau DM, Weiss SR, Holmes KV. Conformational changes in the spike glycoprotein of murine coronavirus are induced at 37 degrees C either by soluble murine CEACAM1 receptors or by pH 8. J Virol 2003; 77: 830–840. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 33. Xiao X, Chakraborti S, Dimitrov AS, Gramatikoff K, Dimitrov DS. The SARS‐CoV S glycoprotein: expression and functional characterization. Biochem Biophys Res Commun 2003; 312: 1159–1164. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 34. He Y, Lu H, Siddiqui P, Zhou Y, Jiang S. Receptor‐binding domain of severe acute respiratory syndrome coronavirus spike protein contains multiple conformation‐dependent epitopes that induce highly potent neutralizing antibodies. J Immunol 2005; 174: 4908–4915. [DOI] [PubMed] [Google Scholar]
  • 35. Sui J, Li W, Murakami A, et al Potent neutralization of severe acute respiratory syndrome (SARS) coronavirus by a human mAb to S1 protein that blocks receptor association. Proc Natl Acad Sci USA 2004; 101: 2536–2541. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 36. van den Brink EN, Ter Meulen J, Cox F, et al Molecular and biological characterization of human monoclonal antibodies binding to the spike and nucleocapsid proteins of severe acute respiratory syndrome coronavirus. J Virol 2005; 79: 1635–1644. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 37. Spiga O, Bernini A, Ciutti A, et al Molecular modelling of S1 and S2 subunits of SARS coronavirus spike glycoprotein. Biochem Biophys Res Commun 2003; 310: 78–83. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 38. Yi CE, Ba L, Zhang L, Ho DD, Chen Z. Single amino acid substitutions in the severe acute respiratory syndrome coronavirus spike glycoprotein determine viral entry and immunogenicity of a major neutralizing domain. J Virol 2005; 79: 11638–11646. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 39. Siddell S, Wege H, Ter Meulen V. The biology of coronaviruses. J Gen Virol 1983; 64(Pt 4): 761–776. [DOI] [PubMed] [Google Scholar]
  • 40. Lai MM, Cavanagh D. The molecular biology of coronaviruses. Adv Virus Res 1997; 48: 1–100. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 41. Liu X, Shi Y, Li P, et al Profile of antibodies to the nucleocapsid protein of the severe acute respiratory syndrome (SARS)‐associated coronavirus in probable SARS patients. Clin Diagn Lab Immunol 2004; 11: 227–228. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 42. Shi Y, Yi Y, Li P, et al Diagnosis of severe acute respiratory syndrome (SARS) by detection of SARS coronavirus nucleocapsid antibodies in an antigen‐capturing enzyme‐linked immunosorbent assay. J Clin Microbiol 2003; 41: 5781–5782. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 43. Chen Z, Pei D, Jiang L, et al Antigenicity analysis of different regions of the severe acute respiratory syndrome coronavirus nucleocapsid protein. Clin Chem 2004; 50: 988–995. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 44. He Y, Zhou Y, Wu H, Kou Z, Liu S, Jiang S. Mapping of antigenic sites on the nucleocapsid protein of the severe acute respiratory syndrome coronavirus. J Clin Microbiol 2004; 42: 5309–5314. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 45. Pang H, Liu Y, Han X, et al Protective humoral responses to severe acute respiratory syndrome‐associated coronavirus: implications for the design of an effective protein‐based vaccine. J Gen Virol 2004; 85: 3109–3113. [DOI] [PubMed] [Google Scholar]
  • 46. Zhong X, Yang H, Guo ZF, et al B‐cell responses in patients who have recovered from severe acute respiratory syndrome target a dominant site in the S2 domain of the surface spike glycoprotein. J Virol 2005; 79: 3401–3408. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 47. Woo PC, Lau SK, Wong BH, et al False‐positive results in a recombinant severe acute respiratory syndrome‐associated coronavirus (SARS‐CoV) nucleocapsid enzyme‐linked immunosorbent assay due to HCoV‐OC43 and HCoV‐229E rectified by Western blotting with recombinant SARS‐CoV spike polypeptide. J Clin Microbiol 2004; 42: 5885–5888. [DOI] [PMC free article] [PubMed] [Google Scholar] [Retracted]
  • 48. Traggiai E, Becker S, Subbarao K, et al An efficient method to make human monoclonal antibodies from memory B cells: potent neutralization of SARS coronavirus. Nat Med 2004; 10: 871–875. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 49. Sui J, Li W, Roberts A, et al Evaluation of human monoclonal antibody 80R for immunoprophylaxis of severe acute respiratory syndrome by an animal study, epitope mapping, and analysis of spike variants. J Virol 2005; 79: 5900–5906. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 50. Peiris JS, Chu CM, Cheng VC, et al Clinical progression and viral load in a community outbreak of coronavirus‐associated SARS pneumonia: a prospective study. Lancet 2003; 361: 1767–1772. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 51. Nie Y, Wang G, Shi X, et al Neutralizing antibodies in patients with severe acute respiratory syndrome‐associated coronavirus infection. J Infect Dis 2004; 190: 1119–1126. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 52. Chen W, Xu Z, Mu J, et al Antibody response and viraemia during the course of severe acute respiratory syndrome (SARS)‐associated coronavirus infection. J Med Microbiol 2004; 53: 435–438. [DOI] [PubMed] [Google Scholar]
  • 53. Wang WK, Chen SY, Liu IJ, et al Detection of SARS‐associated coronavirus in throat wash and saliva in early diagnosis. Emerg Infect Dis 2004; 10: 1213–1219. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 54. Chen W, Xu Z, Mu J, et al Antibody response and viraemia during the course of severe acute respiratory syndrome (SARS)‐associated coronavirus infection. J Med Microbiol 2004; 53: 435–438. [DOI] [PubMed] [Google Scholar]
  • 55. He Q, Manopo I, Lu L, et al Novel immunofluorescence assay using recombinant nucleocapsid‐spike fusion protein as antigen to detect antibodies against severe acute respiratory syndrome coronavirus. Clin Diagn Lab Immunol 2005; 12: 321–328. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 56. Takasuka N, Fujii H, Takahashi Y, et al A subcutaneously injected UV‐inactivated SARS coronavirus vaccine elicits systemic humoral immunity in mice. Int Immunol 2004; 16: 1423–1430. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 57. Di B, Hao W, Gao Y, et al Monoclonal antibody‐based antigen capture enzyme‐linked immunosorbent assay reveals high sensitivity of the nucleocapsid protein in acute‐phase sera of severe acute respiratory syndrome patients. Clin Diagn Lab Immunol 2005; 12: 135–140. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 58. Lau SK, Woo PC, Wong BH, et al Detection of severe acute respiratory syndrome (SARS) coronavirus nucleocapsid protein in sars patients by enzyme‐linked immunosorbent assay. J Clin Microbiol 2004; 42: 2884–2889. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 59. Chan PK, To WK, Liu EY, et al Evaluation of a peptide‐based enzyme immunoassay for anti‐SARS coronavirus IgG antibody. J Med Virol 2004; 74: 517–520. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 60. Martina BE, Haagmans BL, Kuiken T, et al Virology: SARS virus infection of cats and ferrets. Nature 2003; 425: 915. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 61. Leung WK, To KF, Chan PK, et al Enteric involvement of severe acute respiratory syndrome‐associated coronavirus infection. Gastroenterology 2003; 125: 1011–1017. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 62. Wang YD, Sin WY, Xu GB, et al T‐cell epitopes in severe acute respiratory syndrome (SARS) coronavirus spike protein elicit a specific T‐cell immune response in patients who recover from SARS. J Virol 2004; 78: 5612–5618. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 63. Wang B, Chen H, Jiang X, et al Identification of an HLA‐A*0201‐restricted CD8+ T‐cell epitope SSp‐1 of SARS‐CoV spike protein. Blood 2004; 104: 200–206. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 64. Zhi Y, Kobinger GP, Jordan H, et al Identification of murine CD8 T cell epitopes in codon‐optimized SARS‐associated coronavirus spike protein. Virology 2005; 335: 34–45. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 65. Xiong S, Wang YF, Zhang MY, et al Immunogenicity of SARS inactivated vaccine in BALB/c mice. Immunol Lett 2004; 95: 139–143. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 66. Qu D, Zheng B, Yao X, et al Intranasal immunization with inactivated SARS‐CoV (SARS‐associated coronavirus) induced local and serum antibodies in mice. Vaccine 2005; 23: 924–931. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 67. Zhang CH, Lu JH, Wang YF, et al Immune responses in Balb/c mice induced by a candidate SARS‐CoV inactivated vaccine prepared from F69 strain. Vaccine 2005; 23: 3196–3201. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 68. Temperton NJ, Chan PK, Simmons G, et al Longitudinally profiling neutralizing antibody response to SARS coronavirus with pseudotypes. Emerg Infect Dis 2005; 11: 411–416. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 69. Bisht H, Roberts A, Vogel L, et al Severe acute respiratory syndrome coronavirus spike protein expressed by attenuated vaccinia virus protectively immunizes mice. Proc Natl Acad Sci USA 2004; 101: 6641–6646. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 70. Chen Z, Zhang L, Qin C, et al Recombinant modified vaccinia virus Ankara expressing the spike glycoprotein of severe acute respiratory syndrome coronavirus induces protective neutralizing antibodies primarily targeting the receptor binding region. J Virol 2005; 79: 2678–2688. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 71. Weingartl H, Czub M, Czub S, et al Immunization with modified vaccinia virus Ankara‐based recombinant vaccine against severe acute respiratory syndrome is associated with enhanced hepatitis in ferrets. J Virol 2004; 78: 12672–12676. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 72. Chalmers WS, Horsburgh BC, Baxendale W, Brown TD. Enhancement of FIP in cats immunised with vaccinia virus recombinants expressing CCV and TGEV spike glycoproteins. Adv Exp Med Biol 1993; 342: 359–364. [DOI] [PubMed] [Google Scholar]
  • 73. Gao W, Tamin A, Soloff A, et al Effects of a SARS‐associated coronavirus vaccine in monkeys. Lancet 2003; 362: 1895–1896. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 74. Faber M, Lamirande EW, Roberts A, et al A single immunization with a rhabdovirus‐based vector expressing severe acute respiratory syndrome coronavirus (SARS‐CoV) S protein results in the production of high levels of SARS‐CoV‐neutralizing antibodies. J Gen Virol 2005; 86: 1435–1440. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 75. Kapadia SU, Rose JK, Lamirande E, Vogel L, Subbarao K, Roberts A. Long‐term protection from SARS coronavirus infection conferred by a single immunization with an attenuated VSV‐based vaccine. Virology 2005; 3420: 174–182. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 76. Buchholz UJ, Bukreyev A, Yang L, et al Contributions of the structural proteins of severe acute respiratory syndrome coronavirus to protective immunity. Proc Natl Acad Sci USA 2004; 101: 9804–9809. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 77. Bukreyev A, Lamirande EW, Buchholz UJ, et al Mucosal immunisation of African green monkeys (Cercopithecus aethiops) with an attenuated parainfluenza virus expressing the SARS coronavirus spike protein for the prevention of SARS. Lancet 2004; 363: 2122–2127. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 78. Gurunathan S, Klinman DM, Seder RA. DNA Vaccines: immunology, application, and optimization. Annu Rev Immunol 2000; 18: 927–974. [DOI] [PubMed] [Google Scholar]
  • 79. Yang ZY, Kong WP, Huang Y, et al A DNA vaccine induces SARS coronavirus neutralization and protective immunity in mice. Nature 2004; 428: 561–564. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 80. Kim TW, Lee JH, Hung CF, et al Generation and characterization of DNA vaccines targeting the nucleocapsid protein of severe acute respiratory syndrome coronavirus. J Virol 2004; 78: 4638–4645. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 81. Zhu MS, Pan Y, Chen HQ, et al Induction of SARS‐nucleoprotein‐specific immune response by use of DNA vaccine. Immunol Lett 2004; 92: 237–243. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 82. Zhao P, Cao J, Zhao LJ, et al Immune responses against SARS‐coronavirus nucleocapsid protein induced by DNA vaccine. Virology 2005; 331: 128–135. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 83. Woo PC, Lau SK, Tsoi HW, et al SARS coronavirus spike polypeptide DNA vaccine priming with recombinant spike polypeptide from Escherichia coli as booster induces high titer of neutralizing antibody against SARS coronavirus. Vaccine 2005; 23: 4959–4968. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 84. Zakhartchouk AN, Liu Q, Petric M, Babiuk LA. Augmentation of immune responses to SARS coronavirus by a combination of DNA and whole killed virus vaccines. Vaccine 2005; 23: 4385–4391. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 85. Bisht H, Roberts A, Vogel L, Subbarao K, Moss B. Neutralizing antibody and protective immunity to SARS coronavirus. Virology 2005; 334: 160–165. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 86. Chou TH, Wang S, Sakhatskyy PV, et al Epitope mapping and biological function analysis of antibodies produced by immunization of mice with an inactivated Chinese isolate of severe acute respiratory syndrome‐associated coronavirus (SARS‐CoV). Virology 2005; 334: 134–143. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 87. Gubbins MJ, Plummer FA, Yuan XY, et al Molecular characterization of a panel of murine monoclonal antibodies specific for the SARS‐coronavirus. Mol Immunol 2005; 42: 125–136. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 88. Che XY, Qiu LW, Pan YX, et al Sensitive and specific monoclonal antibody‐based capture enzyme immunoassay for detection of nucleocapsid antigen in sera from patients with severe acute respiratory syndrome. J Clin Microbiol 2004; 42: 2629–2635. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 89. Sui J, Li W, Roberts A, et al Evaluation of human monoclonal antibody 80R for immunoprophylaxis of severe acute respiratory syndrome by an animal study, epitope mapping, and analysis of spike variants. J Virol 2005; 79: 5900–5906. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 90. Zakhartchouk AN, Viswanathan S, Mahony JB, Gauldie J, Babiuk LA. Severe acute respiratory syndrome coronavirus nucleocapsid protein expressed by an adenovirus vector is phosphorylated and immunogenic in mice. J Gen Virol 2005; 86: 211–215. [DOI] [PubMed] [Google Scholar]
  • 91. Okada M, Takemoto Y, Okuno Y, et al The development of vaccines against SARS corona virus in mice and SCID‐PBL/hu mice. Vaccine 2005; 23: 2269–2272. [DOI] [PMC free article] [PubMed] [Google Scholar]

Articles from Reviews in Medical Virology are provided here courtesy of Wiley

RESOURCES