Top

Virology Journal

Published in:

Open Access 01-12-2010 | Research

Potent and persistent antibody responses against the receptor-binding domain of SARS-CoV spike protein in recovered patients

Authors: Zhiliang Cao, Lifeng Liu, Lanying Du, Chao Zhang, Shibo Jiang, Taisheng Li, Yuxian He

Published in: Virology Journal | Issue 1/2010

Abstract

Background

The spike (S) protein of SARS-CoV not only mediates receptor-binding but also induces neutralizing antibodies. We previously identified the receptor-binding domain (RBD) of S protein as a major target of neutralizing antibodies in animal models and thus proposed a RBD-based vaccine. However, the antigenicity and immunogenicity of RBD in humans need to be characterized.

Results

Two panels of serum samples from recovered SARS patients were included and the antibody responses against the RBD were measured by ELISA and micro-neutralization assays. We found that the RBD of S protein induced potent antibody responses in the recovered SARS patients and RBD-specific antibodies could persist at high titers over three year follow-up. Furthermore, affinity purified anti-RBD antibodies possessed robust neutralizing activity.

Conclusion

The RBD of SARS-CoV is highly immunogenic in humans and mediates protective responses and RBD-based vaccines and diagnostic approaches can be further developed.

Available only for authorised users

Li W, Shi Z, Yu M, Ren W, Smith C, Epstein JH, Wang H, Crameri G, Hu Z, Zhang H, et al.: Bats are natural reservoirs of SARS-like coronaviruses. Science 2005, 310: 676-679. 10.1126/science.1118391PubMedCrossRef

Rota PA, Oberste MS, Monroe SS, Nix WA, Campagnoli R, Icenogle JP, Penaranda S, Bankamp B, Maher K, Chen MH, et al.: Characterization of a novel coronavirus associated with severe acute respiratory syndrome. Science 2003, 300: 1394-1399. 10.1126/science.1085952PubMedCrossRef

Marra MA, Jones SJ, Astell CR, Holt RA, Brooks-Wilson A, Butterfield YS, Khattra J, Asano JK, Barber SA, Chan SY, et al.: The Genome sequence of the SARS-associated coronavirus. Science 2003, 300: 1399-1404. 10.1126/science.1085953PubMedCrossRef

Liu S, Xiao G, Chen Y, He Y, Niu J, Escalante CR, Xiong H, Farmar J, Debnath AK, Tien P, Jiang S: Interaction between heptad repeat 1 and 2 regions in spike protein of SARS-associated coronavirus: implications for virus fusogenic mechanism and identification of fusion inhibitors. Lancet 2004, 363: 938-947. 10.1016/S0140-6736(04)15788-7PubMedCrossRef

Bosch BJ, Martina BE, Van Der Zee R, Lepault J, Haijema BJ, Versluis C, Heck AJ, De Groot R, Osterhaus AD, Rottier PJ: Severe acute respiratory syndrome coronavirus (SARS-CoV) infection inhibition using spike protein heptad repeat-derived peptides. Proc Natl Acad Sci USA 2004, 101: 8455-8460. 10.1073/pnas.0400576101PubMedPubMedCentralCrossRef

Simmons G, Reeves JD, Rennekamp AJ, Amberg SM, Piefer AJ, Bates P: Characterization of severe acute respiratory syndrome-associated coronavirus (SARS-CoV) spike glycoprotein-mediated viral entry. Proc Natl Acad Sci USA 2004, 101: 4240-4245. 10.1073/pnas.0306446101PubMedPubMedCentralCrossRef

Buchholz UJ, Bukreyev A, Yang L, Lamirande EW, Murphy BR, Subbarao K, Collins PL: Contributions of the structural proteins of severe acute respiratory syndrome coronavirus to protective immunity. Proc Natl Acad Sci USA 2004, 101: 9804-9809. 10.1073/pnas.0403492101PubMedPubMedCentralCrossRef

Yang ZY, Kong WP, Huang Y, Roberts A, Murphy BR, Subbarao K, Nabel GJ: A DNA vaccine induces SARS coronavirus neutralization and protective immunity in mice. Nature 2004, 428: 561-564. 10.1038/nature02463PubMedCrossRef

Bisht H, Roberts A, Vogel L, Bukreyev A, Collins PL, Murphy BR, Subbarao K, Moss B: Severe acute respiratory syndrome coronavirus spike protein expressed by attenuated vaccinia virus protectively immunizes mice. Proc Natl Acad Sci USA 2004, 101: 6641-6646. 10.1073/pnas.0401939101PubMedPubMedCentralCrossRef

10.

Bukreyev A, Lamirande EW, Buchholz UJ, Vogel LN, Elkins WR, St Claire M, Murphy BR, Subbarao K, Collins PL: 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. 10.1016/S0140-6736(04)16501-XPubMedCrossRef

11.

ter Meulen J, Bakker AB, van den Brink EN, Weverling GJ, Martina BE, Haagmans BL, Kuiken T, de Kruif J, Preiser W, Spaan W, et al.: Human monoclonal antibody as prophylaxis for SARS coronavirus infection in ferrets. Lancet 2004, 363: 2139-2141. 10.1016/S0140-6736(04)16506-9PubMedCrossRef

12.

He Y, Zhou Y, Wu H, Luo B, Chen J, Li W, Jiang S: Identification of immunodominant sites on the spike protein of severe acute respiratory syndrome (SARS) coronavirus: implication for developing SARS diagnostics and vaccines. J Immunol 2004, 173: 4050-4057.PubMedCrossRef

13.

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. 10.1074/jbc.C300520200PubMedCrossRef

14.

Babcock GJ, Esshaki DJ, Thomas WD Jr, Ambrosino DM: Amino acids 270 to 510 of the severe acute respiratory syndrome coronavirus spike protein are required for interaction with receptor. J Virol 2004, 78: 4552-4560. 10.1128/JVI.78.9.4552-4560.2004PubMedPubMedCentralCrossRef

15.

Li W, Moore MJ, Vasilieva N, Sui J, Wong SK, Berne MA, Somasundaran M, Sullivan JL, Luzuriaga K, Greenough TC, et al.: Angiotensin-converting enzyme 2 is a functional receptor for the SARS coronavirus. Nature 2003, 426: 450-454. 10.1038/nature02145PubMedCrossRef

16.

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.PubMedCrossRef

17.

He Y, Li J, Li W, Lustigman S, Farzan M, Jiang S: Cross-neutralization of human and palm civet severe acute respiratory syndrome coronaviruses by antibodies targeting the receptor-binding domain of spike protein. J Immunol 2006, 176: 6085-6092.PubMedCrossRef

18.

He Y, Li J, Heck S, Lustigman S, Jiang S: Antigenic and immunogenic characterization of recombinant baculovirus-expressed severe acute respiratory syndrome coronavirus spike protein: implication for vaccine design. J Virol 2006, 80: 5757-5767. 10.1128/JVI.00083-06PubMedPubMedCentralCrossRef

19.

He Y, Zhu Q, Liu S, Zhou Y, Yang B, Li J, Jiang S: Identification of a critical neutralization determinant of severe acute respiratory syndrome (SARS)-associated coronavirus: importance for designing SARS vaccines. Virology 2005, 334: 74-82. 10.1016/j.virol.2005.01.034PubMedCrossRef

20.

Du L, He Y, Zhou Y, Liu S, Zheng BJ, Jiang S: The spike protein of SARS-CoV--a target for vaccine and therapeutic development. Nat Rev Microbiol 2009, 7: 226-236. 10.1038/nrmicro2090PubMedPubMedCentralCrossRef

21.

He Y, Jiang S: Vaccine design for severe acute respiratory syndrome coronavirus. Viral Immunol 2005, 18: 327-332. 10.1089/vim.2005.18.327PubMedCrossRef

22.

Jiang S, He Y, Liu S: SARS vaccine development. Emerg Infect Dis 2005, 11: 1016-1020.PubMedPubMedCentralCrossRef

23.

Du L, Zhao G, Chan CC, Sun S, Chen M, Liu Z, Guo H, He Y, Zhou Y, Zheng BJ, Jiang S: Recombinant receptor-binding domain of SARS-CoV spike protein expressed in mammalian, insect and E. coli cells elicits potent neutralizing antibody and protective immunity. Virology 2009, 393: 144-150. 10.1016/j.virol.2009.07.018PubMedPubMedCentralCrossRef

24.

Du L, Zhao G, He Y, Guo Y, Zheng BJ, Jiang S, Zhou Y: Receptor-binding domain of SARS-CoV spike protein induces long-term protective immunity in an animal model. Vaccine 2007, 25: 2832-2838. 10.1016/j.vaccine.2006.10.031PubMedCrossRef

25.

Du L, Zhao G, Lin Y, Sui H, Chan C, Ma S, He Y, Jiang S, Wu C, Yuen KY, et al.: Intranasal vaccination of recombinant adeno-associated virus encoding receptor-binding domain of severe acute respiratory syndrome coronavirus (SARS-CoV) spike protein induces strong mucosal immune responses and provides long-term protection against SARS-CoV infection. J Immunol 2008, 180: 948-956.PubMedPubMedCentralCrossRef

26.

Zhu Z, Chakraborti S, He Y, Roberts A, Sheahan T, Xiao X, Hensley LE, Prabakaran P, Rockx B, Sidorov IA, et al.: Potent cross-reactive neutralization of SARS coronavirus isolates by human monoclonal antibodies. Proc Natl Acad Sci USA 2007, 104: 12123-12128. 10.1073/pnas.0701000104PubMedPubMedCentralCrossRef

27.

Sui J, Li W, Murakami A, Tamin A, Matthews LJ, Wong SK, Moore MJ, Tallarico AS, Olurinde M, Choe H, 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. 10.1073/pnas.0307140101PubMedPubMedCentralCrossRef

28.

He Y, Li J, Du L, Yan X, Hu G, Zhou Y, Jiang S: Identification and characterization of novel neutralizing epitopes in the receptor-binding domain of SARS-CoV spike protein: revealing the critical antigenic determinants in inactivated SARS-CoV vaccine. Vaccine 2006, 24: 5498-5508. 10.1016/j.vaccine.2006.04.054PubMedCrossRef

29.

He Y, Li J, Jiang S: A single amino acid substitution (R441A) in the receptor-binding domain of SARS coronavirus spike protein disrupts the antigenic structure and binding activity. Biochem Biophys Res Commun 2006, 344: 106-113. 10.1016/j.bbrc.2006.03.139PubMedCrossRef

30.

He Y, Zhou Y, Liu S, Kou Z, Li W, Farzan M, Jiang S: 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. 10.1016/j.bbrc.2004.09.106PubMedCrossRef

31.

He Y, Zhou Y, Siddiqui P, Jiang S: Inactivated SARS-CoV vaccine elicits high titers of spike protein-specific antibodies that block receptor binding and virus entry. Biochem Biophys Res Commun 2004, 325: 445-452. 10.1016/j.bbrc.2004.10.052PubMedCrossRef

32.

He Y, Zhou Y, Siddiqui P, Niu J, Jiang S: Identification of immunodominant epitopes on the membrane protein of the severe acute respiratory syndrome-associated coronavirus. J Clin Microbiol 2005, 43: 3718-3726. 10.1128/JCM.43.8.3718-3726.2005PubMedPubMedCentralCrossRef

33.

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. 10.1128/JCM.42.11.5309-5314.2004PubMedPubMedCentralCrossRef

34.

Du L, Zhao G, Lin Y, Chan C, He Y, Jiang S, Wu C, Jin DY, Yuen KY, Zhou Y, Zheng BJ: Priming with rAAV encoding RBD of SARS-CoV S protein and boosting with RBD-specific peptides for T cell epitopes elevated humoral and cellular immune responses against SARS-CoV infection. Vaccine 2008, 26: 1644-1651. 10.1016/j.vaccine.2008.01.025PubMedPubMedCentralCrossRef

35.

Wu LP, Wang NC, Chang YH, Tian XY, Na DY, Zhang LY, Zheng L, Lan T, Wang LF, Liang GD: Duration of antibody responses after severe acute respiratory syndrome. Emerg Infect Dis 2007, 13: 1562-1564.PubMedPubMedCentralCrossRef

36.

Cao WC, Liu W, Zhang PH, Zhang F, Richardus JH: Disappearance of antibodies to SARS-associated coronavirus after recovery. N Engl J Med 2007, 357: 1162-1163. 10.1056/NEJMc070348PubMedCrossRef

Title: Potent and persistent antibody responses against the receptor-binding domain of SARS-CoV spike protein in recovered patients
Authors: Zhiliang Cao
Lifeng Liu
Lanying Du
Chao Zhang
Shibo Jiang
Taisheng Li
Yuxian He
Publication date: 01-12-2010
Publisher: BioMed Central
Published in: Virology Journal / Issue 1/2010
Electronic ISSN: 1743-422X
DOI: https://doi.org/10.1186/1743-422X-7-299

ACC 2024 Congress Coverage

Heart Failure Video

At a glance: The ONWARDS insulin icodec trials

Springer Medicine

Potent and persistent antibody responses against the receptor-binding domain of SARS-CoV spike protein in recovered patients

Abstract

Background

Results

Conclusion

ACC 2024 Congress Coverage

Year in Review: Heart failure and cardiomyopathies

Semaglutide benefits people with type 2 diabetes and obesity-related heart failure

Incentivised to exercise

New intervention for STEMI-related cardiogenic shock

» View more highlights on the ACC 2024 congress hub page

At a glance: The ONWARDS insulin icodec trials

Springer Medicine

Abstract

Background

Results

Conclusion

Please log in to get access to this content

Other articles of this Issue 1/2010

Upregulation of a novel eukaryotic translation initiation factor 5A (eIF5A) in dengue 2 virus-infected mosquito cells

Multiplex Amplification Refractory Mutation System Polymerase Chain Reaction (ARMS-PCR) for diagnosis of natural infection with canine distemper virus

The expression and significance of protooncogene c-fos in viral myocarditis

Assessing changes in vascular permeability in a hamster model of viral hemorrhagic fever

The novel HSV-1 US5-1 RNA is transcribed off a domain encoding US 5, US 4, US 3, US 2 and α22

Mechanisms of cell entry by human papillomaviruses: an overview

ACC 2024 Congress Coverage

Year in Review: Heart failure and cardiomyopathies

Semaglutide benefits people with type 2 diabetes and obesity-related heart failure

Incentivised to exercise

New intervention for STEMI-related cardiogenic shock

» View more highlights on the ACC 2024 congress hub page