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. 1988 Nov;62(11):4232–4238. doi: 10.1128/jvi.62.11.4232-4238.1988

Neutralization of respiratory syncytial virus by individual and mixtures of F and G protein monoclonal antibodies.

L J Anderson 1, P Bingham 1, J C Hierholzer 1
PMCID: PMC253856  PMID: 2459412

Abstract

We identified several types of neutralization effected by F and G protein monoclonal antibodies (MAbs) reacted individually or as mixtures against respiratory syncytial virus (RSV). Neutralizing activity was identified by a microneutralization test in which virus replication was determined by enzyme immunoassay. Complete neutralization was seen only with MAbs against the F protein. Strain-specific neutralization, complete neutralization against some strains of RSV, and no neutralization against other strains were seen with an additional MAb against the F protein. Partial neutralization, virus replication significantly reduced but still present, and no neutralization were seen with MAbs against both the F and G proteins. Enhanced neutralization, enhanced efficacy of neutralization, or increased neutralizing titer with a mixture of two MAbs over that for the individual MAbs was seen with all MAbs against the F protein and all but three MAbs against the G protein. Most (10 of 13) of the MAbs that exhibited neutralizing activity reacted with some but not all strains of RSV in an enzyme immunoassay. The epitopes corresponding to these 10 MAbs probably contribute to the strain-specific component of the neutralizing antibody response to RSV. Our results suggest that interpretation of RSV neutralization with MAbs is complex and that studies of such neutralization should include mixtures of MAbs and multiple RSV strains.

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Selected References

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

  1. Anderson L. J., Hierholzer J. C., Bingham P. G., Stone Y. O. Microneutralization test for respiratory syncytial virus based on an enzyme immunoassay. J Clin Microbiol. 1985 Dec;22(6):1050–1052. doi: 10.1128/jcm.22.6.1050-1052.1985. [DOI] [PMC free article] [PubMed] [Google Scholar]
  2. Anderson L. J., Hierholzer J. C., Stone Y. O., Tsou C., Fernie B. F. Identification of epitopes on respiratory syncytial virus proteins by competitive binding immunoassay. J Clin Microbiol. 1986 Mar;23(3):475–480. doi: 10.1128/jcm.23.3.475-480.1986. [DOI] [PMC free article] [PubMed] [Google Scholar]
  3. 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]
  4. CHANOCK R., FINBERG L. Recovery from infants with respiratory illness of a virus related to chimpanzee coryza agent (CCA). II. Epidemiologic aspects of infection in infants and young children. Am J Hyg. 1957 Nov;66(3):291–300. doi: 10.1093/oxfordjournals.aje.a119902. [DOI] [PubMed] [Google Scholar]
  5. COATES H. V., CHANOCK R. M. Experimental infection with respiratory syncytial virus in several species of animals. Am J Hyg. 1962 Nov;76:302–312. doi: 10.1093/oxfordjournals.aje.a120285. [DOI] [PubMed] [Google Scholar]
  6. COATES H. V., KENDRICK L., CHANOCK R. M. Antigenic differences between two strains of respiratory syncytial virus. Proc Soc Exp Biol Med. 1963 Apr;112:958–964. doi: 10.3181/00379727-112-28221. [DOI] [PubMed] [Google Scholar]
  7. Chanock R. M., Kapikian A. Z., Mills J., Kim H. W., Parrott R. H. Influence of immunological factors in respiratory syncytial virus disease. Arch Environ Health. 1970 Sep;21(3):347–355. doi: 10.1080/00039896.1970.10667249. [DOI] [PubMed] [Google Scholar]
  8. Cranage M. P., Gardner P. S. Systemic cell-mediated and antibody responses in infants with respiratory syncytial virus infections. J Med Virol. 1980;5(2):161–170. doi: 10.1002/jmv.1890050210. [DOI] [PubMed] [Google Scholar]
  9. Doggett J. E., Taylor-Robinson D. Serological studies with respiratory syncytial virus. Arch Gesamte Virusforsch. 1965;15(5):601–608. doi: 10.1007/BF01245207. [DOI] [PubMed] [Google Scholar]
  10. FORBES J. A., BENNETT N. M., GRAY N. J. Epidemic bronchiolitis caused by a respiratory syncytial virus: clinical aspects. Med J Aust. 1961 Dec 9;48(2):933–935. doi: 10.5694/j.1326-5377.1961.tb70132.x. [DOI] [PubMed] [Google Scholar]
  11. Fernald G. W., Almond J. R., Henderson F. W. Cellular and humoral immunity in recurrent respiratory syncytial virus infections. Pediatr Res. 1983 Sep;17(9):753–758. doi: 10.1203/00006450-198309000-00014. [DOI] [PubMed] [Google Scholar]
  12. Fernie B. F., Cote P. J., Jr, Gerin J. L. Classification of hybridomas to respiratory syncytial virus glycoproteins. Proc Soc Exp Biol Med. 1982 Dec;171(3):266–271. doi: 10.3181/00379727-171-41509. [DOI] [PubMed] [Google Scholar]
  13. Hall C. B., Powell K. R., MacDonald N. E., Gala C. L., Menegus M. E., Suffin S. C., Cohen H. J. Respiratory syncytial viral infection in children with compromised immune function. N Engl J Med. 1986 Jul 10;315(2):77–81. doi: 10.1056/NEJM198607103150201. [DOI] [PubMed] [Google Scholar]
  14. 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]
  15. 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]
  16. King A. M., Stott E. J., Langer S. J., Young K. K., Ball L. A., Wertz G. W. Recombinant vaccinia viruses carrying the N gene of human respiratory syncytial virus: studies of gene expression in cell culture and immune response in mice. J Virol. 1987 Sep;61(9):2885–2890. doi: 10.1128/jvi.61.9.2885-2890.1987. [DOI] [PMC free article] [PubMed] [Google Scholar]
  17. Kingsford L. Enhanced neutralization of La Crosse virus by the binding of specific pairs of monoclonal antibodies to the G1 glycoprotein. Virology. 1984 Jul 30;136(2):265–273. doi: 10.1016/0042-6822(84)90163-6. [DOI] [PubMed] [Google Scholar]
  18. Lamprecht C. L., Krause H. E., Mufson M. A. Role of maternal antibody in pneumonia and bronchiolitis due to respiratory syncytial virus. J Infect Dis. 1976 Sep;134(3):211–217. doi: 10.1093/infdis/134.3.211. [DOI] [PubMed] [Google Scholar]
  19. Massey R. J., Schochetman G. Viral epitopes and monoclonal antibodies: isolation of blocking antibodies that inhibit virus neutralization. Science. 1981 Jul 24;213(4506):447–449. doi: 10.1126/science.6264601. [DOI] [PubMed] [Google Scholar]
  20. Mufson M. A., Orvell C., Rafnar B., Norrby E. Two distinct subtypes of human respiratory syncytial virus. J Gen Virol. 1985 Oct;66(Pt 10):2111–2124. doi: 10.1099/0022-1317-66-10-2111. [DOI] [PubMed] [Google Scholar]
  21. Ogilvie M. M., Vathenen A. S., Radford M., Codd J., Key S. Maternal antibody and respiratory syncytial virus infection in infancy. J Med Virol. 1981;7(4):263–271. doi: 10.1002/jmv.1890070403. [DOI] [PubMed] [Google Scholar]
  22. Olmsted R. A., Elango N., Prince G. A., Murphy B. R., Johnson P. R., Moss B., Chanock R. M., Collins P. L. Expression of the F glycoprotein of respiratory syncytial virus by a recombinant vaccinia virus: comparison of the individual contributions of the F and G glycoproteins to host immunity. Proc Natl Acad Sci U S A. 1986 Oct;83(19):7462–7466. doi: 10.1073/pnas.83.19.7462. [DOI] [PMC free article] [PubMed] [Google Scholar]
  23. Orvell C., Norrby E., Mufson M. A. Preparation and characterization of monoclonal antibodies directed against five structural components of human respiratory syncytial virus subgroup B. J Gen Virol. 1987 Dec;68(Pt 12):3125–3135. doi: 10.1099/0022-1317-68-12-3125. [DOI] [PubMed] [Google Scholar]
  24. 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]
  25. Prince G. A., Horswood R. L., Chanock R. M. Quantitative aspects of passive immunity to respiratory syncytial virus infection in infant cotton rats. J Virol. 1985 Sep;55(3):517–520. doi: 10.1128/jvi.55.3.517-520.1985. [DOI] [PMC free article] [PubMed] [Google Scholar]
  26. Stott E. J., Ball L. A., Young K. K., Furze J., Wertz G. W. Human respiratory syncytial virus glycoprotein G expressed from a recombinant vaccinia virus vector protects mice against live-virus challenge. J Virol. 1986 Nov;60(2):607–613. doi: 10.1128/jvi.60.2.607-613.1986. [DOI] [PMC free article] [PubMed] [Google Scholar]
  27. Stott E. J., Taylor G., Ball L. A., Anderson K., Young K. K., King A. M., Wertz G. W. Immune and histopathological responses in animals vaccinated with recombinant vaccinia viruses that express individual genes of human respiratory syncytial virus. J Virol. 1987 Dec;61(12):3855–3861. doi: 10.1128/jvi.61.12.3855-3861.1987. [DOI] [PMC free article] [PubMed] [Google Scholar]
  28. Taylor G., Stott E. J., Bew M., Fernie B. F., Cote P. J., Collins A. P., Hughes M., Jebbett J. Monoclonal antibodies protect against respiratory syncytial virus infection in mice. Immunology. 1984 May;52(1):137–142. [PMC free article] [PubMed] [Google Scholar]
  29. Tyeryar F. J. Report of a workshop on respiratory syncytial virus and parainfluenza viruses. J Infect Dis. 1983 Sep;148(3):588–598. doi: 10.1093/infdis/148.3.588. [DOI] [PubMed] [Google Scholar]
  30. Volk W. A., Synder R. M., Benjamin D. C., Wagner R. R. Monoclonal antibodies to the glycoprotein of vesicular stomatitis virus: comparative neutralizing activity. J Virol. 1982 Apr;42(1):220–227. doi: 10.1128/jvi.42.1.220-227.1982. [DOI] [PMC free article] [PubMed] [Google Scholar]
  31. Walsh E. E., Cote P. J., Fernie B. F., Schlesinger J. J., Brandriss M. W. Analysis of the respiratory syncytial virus fusion protein using monoclonal and polyclonal antibodies. J Gen Virol. 1986 Mar;67(Pt 3):505–513. doi: 10.1099/0022-1317-67-3-505. [DOI] [PubMed] [Google Scholar]
  32. Walsh E. E., Hall C. B., Briselli M., Brandriss M. W., Schlesinger J. J. Immunization with glycoprotein subunits of respiratory syncytial virus to protect cotton rats against viral infection. J Infect Dis. 1987 Jun;155(6):1198–1204. doi: 10.1093/infdis/155.6.1198. [DOI] [PubMed] [Google Scholar]
  33. Walsh E. E., Hruska J. Monoclonal antibodies to respiratory syncytial virus proteins: identification of the fusion protein. J Virol. 1983 Jul;47(1):171–177. doi: 10.1128/jvi.47.1.171-177.1983. [DOI] [PMC free article] [PubMed] [Google Scholar]
  34. 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]
  35. Wertz G. W., Stott E. J., Young K. K., Anderson K., Ball L. A. Expression of the fusion protein of human respiratory syncytial virus from recombinant vaccinia virus vectors and protection of vaccinated mice. J Virol. 1987 Feb;61(2):293–301. doi: 10.1128/jvi.61.2.293-301.1987. [DOI] [PMC free article] [PubMed] [Google Scholar]

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