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Molecular and biological characterization of human monoclonal antibodies binding to the spike and nucleocapsid proteins of severe acute respiratory syndrome coronavirus.
J Virol. 2005 Feb; 79(3):1635-44.JV

Abstract

Human monoclonal antibodies (MAbs) were selected from semisynthetic antibody phage display libraries by using whole irradiated severe acute respiratory syndrome (SARS) coronavirus (CoV) virions as target. We identified eight human MAbs binding to virus and infected cells, six of which could be mapped to two SARS-CoV structural proteins: the nucleocapsid (N) and spike (S) proteins. Two MAbs reacted with N protein. One of the N protein MAbs recognized a linear epitope conserved between all published human and animal SARS-CoV isolates, and the other bound to a nonlinear N epitope. These two N MAbs did not compete for binding to SARS-CoV. Four MAbs reacted with the S glycoprotein, and three of these MAbs neutralized SARS-CoV in vitro. All three neutralizing anti-S MAbs bound a recombinant S1 fragment comprising residues 318 to 510, a region previously identified as the SARS-CoV S receptor binding domain; the nonneutralizing MAb did not. Two strongly neutralizing anti-S1 MAbs blocked the binding of a recombinant S fragment (residues 1 to 565) to SARS-CoV-susceptible Vero cells completely, whereas a poorly neutralizing S1 MAb blocked binding only partially. The MAb ability to block S1-receptor binding and the level of neutralization of the two strongly neutralizing S1 MAbs correlated with the binding affinity to the S1 domain. Finally, epitope mapping, using recombinant S fragments (residues 318 to 510) containing naturally occurring mutations, revealed the importance of residue N479 for the binding of the most potent neutralizing MAb, CR3014. The complete set of SARS-CoV MAbs described here may be useful for diagnosis, chemoprophylaxis, and therapy of SARS-CoV infection and disease.

Authors+Show Affiliations

Crucell Holland BV, PO Box 2048, 2301 CA Leiden, The Netherlands.No affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Journal Article

Language

eng

PubMed ID

15650189

Citation

van den Brink, Edward N., et al. "Molecular and Biological Characterization of Human Monoclonal Antibodies Binding to the Spike and Nucleocapsid Proteins of Severe Acute Respiratory Syndrome Coronavirus." Journal of Virology, vol. 79, no. 3, 2005, pp. 1635-44.
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(3):1635-44.
van den Brink, E. N., Ter Meulen, J., Cox, F., Jongeneelen, M. A., Thijsse, A., Throsby, M., Marissen, W. E., Rood, P. M., Bakker, A. B., Gelderblom, H. R., Martina, B. E., Osterhaus, A. D., Preiser, W., Doerr, H. W., de Kruif, J., & Goudsmit, J. (2005). Molecular and biological characterization of human monoclonal antibodies binding to the spike and nucleocapsid proteins of severe acute respiratory syndrome coronavirus. Journal of Virology, 79(3), 1635-44.
van den Brink EN, 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(3):1635-44. PubMed PMID: 15650189.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Molecular and biological characterization of human monoclonal antibodies binding to the spike and nucleocapsid proteins of severe acute respiratory syndrome coronavirus. AU - van den Brink,Edward N, AU - Ter Meulen,Jan, AU - Cox,Freek, AU - Jongeneelen,Mandy A C, AU - Thijsse,Alexandra, AU - Throsby,Mark, AU - Marissen,Wilfred E, AU - Rood,Pauline M L, AU - Bakker,Alexander B H, AU - Gelderblom,Hans R, AU - Martina,Byron E, AU - Osterhaus,Albert D M E, AU - Preiser,Wolfgang, AU - Doerr,Hans Wilhelm, AU - de Kruif,John, AU - Goudsmit,Jaap, PY - 2005/1/15/pubmed PY - 2005/2/11/medline PY - 2005/1/15/entrez SP - 1635 EP - 44 JF - Journal of virology JO - J Virol VL - 79 IS - 3 N2 - Human monoclonal antibodies (MAbs) were selected from semisynthetic antibody phage display libraries by using whole irradiated severe acute respiratory syndrome (SARS) coronavirus (CoV) virions as target. We identified eight human MAbs binding to virus and infected cells, six of which could be mapped to two SARS-CoV structural proteins: the nucleocapsid (N) and spike (S) proteins. Two MAbs reacted with N protein. One of the N protein MAbs recognized a linear epitope conserved between all published human and animal SARS-CoV isolates, and the other bound to a nonlinear N epitope. These two N MAbs did not compete for binding to SARS-CoV. Four MAbs reacted with the S glycoprotein, and three of these MAbs neutralized SARS-CoV in vitro. All three neutralizing anti-S MAbs bound a recombinant S1 fragment comprising residues 318 to 510, a region previously identified as the SARS-CoV S receptor binding domain; the nonneutralizing MAb did not. Two strongly neutralizing anti-S1 MAbs blocked the binding of a recombinant S fragment (residues 1 to 565) to SARS-CoV-susceptible Vero cells completely, whereas a poorly neutralizing S1 MAb blocked binding only partially. The MAb ability to block S1-receptor binding and the level of neutralization of the two strongly neutralizing S1 MAbs correlated with the binding affinity to the S1 domain. Finally, epitope mapping, using recombinant S fragments (residues 318 to 510) containing naturally occurring mutations, revealed the importance of residue N479 for the binding of the most potent neutralizing MAb, CR3014. The complete set of SARS-CoV MAbs described here may be useful for diagnosis, chemoprophylaxis, and therapy of SARS-CoV infection and disease. SN - 0022-538X UR - https://www.unboundmedicine.com/medline/citation/15650189/Molecular_and_biological_characterization_of_human_monoclonal_antibodies_binding_to_the_spike_and_nucleocapsid_proteins_of_severe_acute_respiratory_syndrome_coronavirus_ L2 - https://journals.asm.org/doi/10.1128/JVI.79.3.1635-1644.2005?url_ver=Z39.88-2003&rfr_id=ori:rid:crossref.org&rfr_dat=cr_pub=pubmed DB - PRIME DP - Unbound Medicine ER -