Skip to main content
NCBI home page
Clinical and Diagnostic Laboratory Immunology logoLink to Clinical and Diagnostic Laboratory Immunology
. 1994 Nov;1(6):701–706. doi: 10.1128/cdli.1.6.701-706.1994

Isolation and characterization of a chimpanzee monoclonal antibody to the G glycoprotein of human respiratory syncytial virus.

J E Crowe Jr 1, P Y Cheung 1, E F Wallace 1, R M Chanock 1, J W Larrick 1, B R Murphy 1, K Fry 1
PMCID: PMC368396  PMID: 8556524

Abstract

Respiratory syncytial virus (RSV) is the most common cause of serious lower respiratory tract disease in infants and young children. In this study a hybridoma line secreting a chimpanzee monoclonal antibody that neutralizes RSV was isolated. Two chimpanzees were immunized with recombinant vaccinia viruses that express the RSV F or G surface glycoprotein and 1 month later were infected intranasally with the wild-type RSV strain A2. Peripheral blood lymphocytes obtained from the animals were transformed with Epstein-Barr virus, and lymphoblastoid cell lines that secreted anti-RSV antibodies were identified by an RSV antigen-binding enzyme-linked immunosorbent assay. Supernatants from RSV antibody-secreting lymphoblastoid cell lines were tested for in vitro virus neutralization before being fused to the heteromyeloma cell GLI-H7. A chimpanzee antibody [immunoglobulin G3(lambda) subclass] produced from a hybridoma line designated E1.4/2 was shown to bind to the RSV G glycoprotein and neutralize a panel of subgroup A viruses, but not subgroup B viruses, at low (nanomolar) concentrations. Mice passively immunized with this antibody were partially resistant to RSV strain A2 challenge. The usefulness of such antibodies in immunoprophylaxis and immunotherapy of RSV infection is discussed.

Full text

PDF
701

Selected References

These references are in PubMed. This may not be the complete list of references from this article.

  1. Anderson L. J., Bingham P., Hierholzer J. C. Neutralization of respiratory syncytial virus by individual and mixtures of F and G protein monoclonal antibodies. J Virol. 1988 Nov;62(11):4232–4238. doi: 10.1128/jvi.62.11.4232-4238.1988. [DOI] [PMC free article] [PubMed] [Google Scholar]
  2. Anderson L. J., Hierholzer J. C., Tsou C., Hendry R. M., Fernie B. F., Stone Y., McIntosh K. Antigenic characterization of respiratory syncytial virus strains with monoclonal antibodies. J Infect Dis. 1985 Apr;151(4):626–633. doi: 10.1093/infdis/151.4.626. [DOI] [PubMed] [Google Scholar]
  3. Barbas C. F., 3rd, Crowe J. E., Jr, Cababa D., Jones T. M., Zebedee S. L., Murphy B. R., Chanock R. M., Burton D. R. Human monoclonal Fab fragments derived from a combinatorial library bind to respiratory syncytial virus F glycoprotein and neutralize infectivity. Proc Natl Acad Sci U S A. 1992 Nov 1;89(21):10164–10168. doi: 10.1073/pnas.89.21.10164. [DOI] [PMC free article] [PubMed] [Google Scholar]
  4. Carroll W. L., Thielemans K., Dilley J., Levy R. Mouse x human heterohybridomas as fusion partners with human B cell tumors. J Immunol Methods. 1986 May 1;89(1):61–72. doi: 10.1016/0022-1759(86)90032-3. [DOI] [PubMed] [Google Scholar]
  5. Coates H. V., Alling D. W., Chanock R. M. An antigenic analysis of respiratory syncytial virus isolates by a plaque reduction neutralization test. Am J Epidemiol. 1966 Mar;83(2):299–313. doi: 10.1093/oxfordjournals.aje.a120586. [DOI] [PubMed] [Google Scholar]
  6. Crowe J. E., Jr, Collins P. L., London W. T., Chanock R. M., Murphy B. R. A comparison in chimpanzees of the immunogenicity and efficacy of live attenuated respiratory syncytial virus (RSV) temperature-sensitive mutant vaccines and vaccinia virus recombinants that express the surface glycoproteins of RSV. Vaccine. 1993 Nov;11(14):1395–1404. doi: 10.1016/0264-410x(93)90168-w. [DOI] [PubMed] [Google Scholar]
  7. Ehrlich P. H., Moustafa Z. A., Harfeldt K. E., Isaacson C., Ostberg L. Potential of primate monoclonal antibodies to substitute for human antibodies: nucleotide sequence of chimpanzee Fab fragments. Hum Antibodies Hybridomas. 1990;1(1):23–26. [PubMed] [Google Scholar]
  8. Ehrlich P. H., Moustafa Z. A., Ostberg L. Nucleotide sequence of chimpanzee Fc and hinge regions. Mol Immunol. 1991 Apr-May;28(4-5):319–322. doi: 10.1016/0161-5890(91)90143-8. [DOI] [PubMed] [Google Scholar]
  9. Groothuis J. R., Simoes E. A., Levin M. J., Hall C. B., Long C. E., Rodriguez W. J., Arrobio J., Meissner H. C., Fulton D. R., Welliver R. C. Prophylactic administration of respiratory syncytial virus immune globulin to high-risk infants and young children. The Respiratory Syncytial Virus Immune Globulin Study Group. N Engl J Med. 1993 Nov 18;329(21):1524–1530. doi: 10.1056/NEJM199311183292102. [DOI] [PubMed] [Google Scholar]
  10. Harrington R. D., Hooton T. M., Hackman R. C., Storch G. A., Osborne B., Gleaves C. A., Benson A., Meyers J. D. An outbreak of respiratory syncytial virus in a bone marrow transplant center. J Infect Dis. 1992 Jun;165(6):987–993. doi: 10.1093/infdis/165.6.987. [DOI] [PubMed] [Google Scholar]
  11. Hemming V. G., Rodriguez W., Kim H. W., Brandt C. D., Parrott R. H., Burch B., Prince G. A., Baron P. A., Fink R. J., Reaman G. Intravenous immunoglobulin treatment of respiratory syncytial virus infections in infants and young children. Antimicrob Agents Chemother. 1987 Dec;31(12):1882–1886. doi: 10.1128/aac.31.12.1882. [DOI] [PMC free article] [PubMed] [Google Scholar]
  12. Iorio R. M., Bratt M. A. Neutralization of Newcastle disease virus by monoclonal antibodies to the hemagglutinin-neuraminidase glycoprotein: requirement for antibodies to four sites for complete neutralization. J Virol. 1984 Aug;51(2):445–451. doi: 10.1128/jvi.51.2.445-451.1984. [DOI] [PMC free article] [PubMed] [Google Scholar]
  13. Johnson P. R., Jr, Olmsted R. A., Prince G. A., Murphy B. R., Alling D. W., Walsh E. E., Collins P. L. Antigenic relatedness between glycoproteins of human respiratory syncytial virus subgroups A and B: evaluation of the contributions of F and G glycoproteins to immunity. J Virol. 1987 Oct;61(10):3163–3166. doi: 10.1128/jvi.61.10.3163-3166.1987. [DOI] [PMC free article] [PubMed] [Google Scholar]
  14. Johnson P. R., Spriggs M. K., Olmsted R. A., Collins P. L. The G glycoprotein of human respiratory syncytial viruses of subgroups A and B: extensive sequence divergence between antigenically related proteins. Proc Natl Acad Sci U S A. 1987 Aug;84(16):5625–5629. doi: 10.1073/pnas.84.16.5625. [DOI] [PMC free article] [PubMed] [Google Scholar]
  15. King M. C., Wilson A. C. Evolution at two levels in humans and chimpanzees. Science. 1975 Apr 11;188(4184):107–116. doi: 10.1126/science.1090005. [DOI] [PubMed] [Google Scholar]
  16. Lang A. B., Bruderer U., Senyk G., Pitt T. L., Larrick J. W., Cryz S. J., Jr Human monoclonal antibodies specific for capsular polysaccharides of Klebsiella recognize clusters of multiple serotypes. J Immunol. 1991 May 1;146(9):3160–3164. [PubMed] [Google Scholar]
  17. Murphy B. R., Sotnikov A. V., Lawrence L. A., Banks S. M., Prince G. A. Enhanced pulmonary histopathology is observed in cotton rats immunized with formalin-inactivated respiratory syncytial virus (RSV) or purified F glycoprotein and challenged with RSV 3-6 months after immunization. Vaccine. 1990 Oct;8(5):497–502. doi: 10.1016/0264-410x(90)90253-i. [DOI] [PubMed] [Google Scholar]
  18. Parrott R. H., Kim H. W., Arrobio J. O., Hodes D. S., Murphy B. R., Brandt C. D., Camargo E., Chanock R. M. Epidemiology of respiratory syncytial virus infection in Washington, D.C. II. Infection and disease with respect to age, immunologic status, race and sex. Am J Epidemiol. 1973 Oct;98(4):289–300. doi: 10.1093/oxfordjournals.aje.a121558. [DOI] [PubMed] [Google Scholar]
  19. Prince A. M., Horowitz B., Baker L., Shulman R. W., Ralph H., Valinsky J., Cundell A., Brotman B., Boehle W., Rey F. Failure of a human immunodeficiency virus (HIV) immune globulin to protect chimpanzees against experimental challenge with HIV. Proc Natl Acad Sci U S A. 1988 Sep;85(18):6944–6948. doi: 10.1073/pnas.85.18.6944. [DOI] [PMC free article] [PubMed] [Google Scholar]
  20. Prince G. A., Hemming V. G., Horswood R. L., Chanock R. M. Immunoprophylaxis and immunotherapy of respiratory syncytial virus infection in the cotton rat. Virus Res. 1985 Oct;3(3):193–206. doi: 10.1016/0168-1702(85)90045-0. [DOI] [PubMed] [Google Scholar]
  21. Prince G. A., Jenson A. B., Horswood R. L., Camargo E., Chanock R. M. The pathogenesis of respiratory syncytial virus infection in cotton rats. Am J Pathol. 1978 Dec;93(3):771–791. [PMC free article] [PubMed] [Google Scholar]
  22. Shawler D. L., Bartholomew R. M., Smith L. M., Dillman R. O. Human immune response to multiple injections of murine monoclonal IgG. J Immunol. 1985 Aug;135(2):1530–1535. [PubMed] [Google Scholar]
  23. Tempest P. R., Bremner P., Lambert M., Taylor G., Furze J. M., Carr F. J., Harris W. J. Reshaping a human monoclonal antibody to inhibit human respiratory syncytial virus infection in vivo. Biotechnology (N Y) 1991 Mar;9(3):266–271. doi: 10.1038/nbt0391-266. [DOI] [PubMed] [Google Scholar]
  24. Towbin H., Staehelin T., Gordon J. Electrophoretic transfer of proteins from polyacrylamide gels to nitrocellulose sheets: procedure and some applications. Proc Natl Acad Sci U S A. 1979 Sep;76(9):4350–4354. doi: 10.1073/pnas.76.9.4350. [DOI] [PMC free article] [PubMed] [Google Scholar]
  25. Walsh E. E., Brandriss M. W., Schlesinger J. J. Purification and characterization of the respiratory syncytial virus fusion protein. J Gen Virol. 1985 Mar;66(Pt 3):409–415. doi: 10.1099/0022-1317-66-3-409. [DOI] [PubMed] [Google Scholar]
  26. Walsh E. E., Schlesinger J. J., Brandriss M. W. Protection from respiratory syncytial virus infection in cotton rats by passive transfer of monoclonal antibodies. Infect Immun. 1984 Feb;43(2):756–758. doi: 10.1128/iai.43.2.756-758.1984. [DOI] [PMC free article] [PubMed] [Google Scholar]
  27. Walsh E. E., Schlesinger J. J., Brandriss M. W. Purification and characterization of GP90, one of the envelope glycoproteins of respiratory syncytial virus. J Gen Virol. 1984 Apr;65(Pt 4):761–767. doi: 10.1099/0022-1317-65-4-761. [DOI] [PubMed] [Google Scholar]

Articles from Clinical and Diagnostic Laboratory Immunology are provided here courtesy of American Society for Microbiology (ASM)

RESOURCES