Skip to main content
Journal of Virology logoLink to Journal of Virology
. 1993 Mar;67(3):1503–1510. doi: 10.1128/jvi.67.3.1503-1510.1993

Bovine respiratory syncytial virus protects cotton rats against human respiratory syncytial virus infection.

F M Piazza 1, S A Johnson 1, M E Darnell 1, D D Porter 1, V G Hemming 1, G A Prince 1
PMCID: PMC237520  PMID: 8437227

Abstract

Human respiratory syncytial virus (HRSV) is the most frequent cause of severe respiratory infections in infancy. No vaccine against this virus has yet been protective, and antiviral drugs have been of limited utility. Using the cotton rat model of HRSV infection, we examined bovine respiratory syncytial virus (BRSV), a cause of acute respiratory disease in young cattle, as a possible vaccine candidate to protect children against HRSV infection. Cotton rats were primed intranasally with graded doses of BRSV/375 or HRSV/Long or were left unprimed. Three weeks later, they were challenged intranasally with either BRSV/375, HRSV/Long (subgroup A), or HRSV/18537 (subgroup B). At intervals postchallenge, animals were sacrificed for virus titration and histologic evaluation. Serum neutralizing antibody titers were determined at the time of viral challenge. BRSV/375 replicated to low titers in nasal tissues and lungs. Priming with 10(5) PFU of BRSV/375 effected a 500- to 1,000-fold reduction in peak nasal HRSV titer and a greater than 1,000-fold reduction in peak pulmonary HRSV titer upon challenge with HRSV/Long or HRSV/18537. In contrast to priming with HRSV, priming with BRSV did not induce substantial levels of neutralizing antibody against HRSV and was associated with a delayed onset of clearance of HRSV upon challenge. Priming with BRSV/375 caused mild nasal and pulmonary pathology and did not cause exacerbation of disease upon challenge with HRSV/Long. Our findings suggest that BRSV may be a potential vaccine against HRSV and a useful tool for studying the mechanisms of immunity to HRSV.

Full text

PDF
1504

Selected References

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

  1. ARCHETTI I., HORSFALL F. L., Jr Persistent antigenic variation of influenza A viruses after incomplete neutralization in ovo with heterologous immune serum. J Exp Med. 1950 Nov 1;92(5):441–462. doi: 10.1084/jem.92.5.441. [DOI] [PMC free article] [PubMed] [Google Scholar]
  2. BLOUNT R. E., Jr, MORRIS J. A., SAVAGE R. E. Recovery of cytopathogenic agent from chimpanzees with coryza. Proc Soc Exp Biol Med. 1956 Jul;92(3):544–549. doi: 10.3181/00379727-92-22538. [DOI] [PubMed] [Google Scholar]
  3. Belshe R. B., Van Voris L. P., Mufson M. A. Parenteral administration of live respiratory syncytial virus vaccine: results of a field trial. J Infect Dis. 1982 Mar;145(3):311–319. doi: 10.1093/infdis/145.3.311. [DOI] [PubMed] [Google Scholar]
  4. Brideau R. J., Walters R. R., Stier M. A., Wathen M. W. Protection of cotton rats against human respiratory syncytial virus by vaccination with a novel chimeric FG glycoprotein. J Gen Virol. 1989 Oct;70(Pt 10):2637–2644. doi: 10.1099/0022-1317-70-10-2637. [DOI] [PubMed] [Google Scholar]
  5. Buynak E. B., Weibel R. E., McLean A. A., Hilleman M. R. Live respiratory syncytial virus vaccine administered parenterally. Proc Soc Exp Biol Med. 1978 Apr;157(4):636–642. doi: 10.3181/00379727-157-40112. [DOI] [PubMed] [Google Scholar]
  6. CHANOCK R., ROIZMAN B., MYERS R. Recovery from infants with respiratory illness of a virus related to chimpanzee coryza agent (CCA). I. Isolation, properties and characterization. Am J Hyg. 1957 Nov;66(3):281–290. doi: 10.1093/oxfordjournals.aje.a119901. [DOI] [PubMed] [Google Scholar]
  7. Chanock R. M., Murphy B. R., Collins P. L., Coelingh K. V., Olmsted R. A., Snyder M. H., Spriggs M. K., Prince G. A., Moss B., Flores J. Live viral vaccines for respiratory and enteric tract diseases. Vaccine. 1988 Apr;6(2):129–133. doi: 10.1016/s0264-410x(88)80014-8. [DOI] [PubMed] [Google Scholar]
  8. Chin J., Magoffin R. L., Shearer L. A., Schieble J. H., Lennette E. H. Field evaluation of a respiratory syncytial virus vaccine and a trivalent parainfluenza virus vaccine in a pediatric population. Am J Epidemiol. 1969 Apr;89(4):449–463. doi: 10.1093/oxfordjournals.aje.a120957. [DOI] [PubMed] [Google Scholar]
  9. Connors M., Collins P. L., Firestone C. Y., Sotnikov A. V., Waitze A., Davis A. R., Hung P. P., Chanock R. M., Murphy B. R. Cotton rats previously immunized with a chimeric RSV FG glycoprotein develop enhanced pulmonary pathology when infected with RSV, a phenomenon not encountered following immunization with vaccinia--RSV recombinants or RSV. Vaccine. 1992;10(7):475–484. doi: 10.1016/0264-410x(92)90397-3. [DOI] [PubMed] [Google Scholar]
  10. Elango N., Prince G. A., Murphy B. R., Venkatesan S., Chanock R. M., Moss B. Resistance to human respiratory syncytial virus (RSV) infection induced by immunization of cotton rats with a recombinant vaccinia virus expressing the RSV G glycoprotein. Proc Natl Acad Sci U S A. 1986 Mar;83(6):1906–1910. doi: 10.1073/pnas.83.6.1906. [DOI] [PMC free article] [PubMed] [Google Scholar]
  11. Fulginiti V. A., Eller J. J., Sieber O. F., Joyner J. W., Minamitani M., Meiklejohn G. Respiratory virus immunization. I. A field trial of two inactivated respiratory virus vaccines; an aqueous trivalent parainfluenza virus vaccine and an alum-precipitated respiratory syncytial virus vaccine. Am J Epidemiol. 1969 Apr;89(4):435–448. doi: 10.1093/oxfordjournals.aje.a120956. [DOI] [PubMed] [Google Scholar]
  12. Jacobs J. W., Edington N. Experimental infection of calves with respiratory syncytial virus. Res Vet Sci. 1975 May;18(3):299–306. [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. Kapikian A. Z., Mitchell R. H., Chanock R. M., Shvedoff R. A., Stewart C. E. An epidemiologic study of altered clinical reactivity to respiratory syncytial (RS) virus infection in children previously vaccinated with an inactivated RS virus vaccine. Am J Epidemiol. 1969 Apr;89(4):405–421. doi: 10.1093/oxfordjournals.aje.a120954. [DOI] [PubMed] [Google Scholar]
  15. Kim H. W., Arrobio J. O., Brandt C. D., Wright P., Hodes D., Chanock R. M., Parrott R. H. Safety and antigenicity of temperature sensitive (TS) mutant respiratory syncytial virus (RSV) in infants and children. Pediatrics. 1973 Jul;52(1):56–63. [PubMed] [Google Scholar]
  16. Kim H. W., Canchola J. G., Brandt C. D., Pyles G., Chanock R. M., Jensen K., Parrott R. H. Respiratory syncytial virus disease in infants despite prior administration of antigenic inactivated vaccine. Am J Epidemiol. 1969 Apr;89(4):422–434. doi: 10.1093/oxfordjournals.aje.a120955. [DOI] [PubMed] [Google Scholar]
  17. Kimman T. G., Westenbrink F. Immunity to human and bovine respiratory syncytial virus. Arch Virol. 1990;112(1-2):1–25. doi: 10.1007/BF01348982. [DOI] [PubMed] [Google Scholar]
  18. Lehmkuhl H. D., Gough P. M., Reed D. E. Characterization and identification of a bovine respiratory syncytial virus isolated from young calves. Am J Vet Res. 1979 Jan;40(1):124–126. [PubMed] [Google Scholar]
  19. Lerch R. A., Anderson K., Wertz G. W. Nucleotide sequence analysis and expression from recombinant vectors demonstrate that the attachment protein G of bovine respiratory syncytial virus is distinct from that of human respiratory syncytial virus. J Virol. 1990 Nov;64(11):5559–5569. doi: 10.1128/jvi.64.11.5559-5569.1990. [DOI] [PMC free article] [PubMed] [Google Scholar]
  20. Lerch R. A., Stott E. J., Wertz G. W. Characterization of bovine respiratory syncytial virus proteins and mRNAs and generation of cDNA clones to the viral mRNAs. J Virol. 1989 Feb;63(2):833–840. doi: 10.1128/jvi.63.2.833-840.1989. [DOI] [PMC free article] [PubMed] [Google Scholar]
  21. Murphy B. R., Olmsted R. A., Collins P. L., Chanock R. M., Prince G. A. Passive transfer of respiratory syncytial virus (RSV) antiserum suppresses the immune response to the RSV fusion (F) and large (G) glycoproteins expressed by recombinant vaccinia viruses. J Virol. 1988 Oct;62(10):3907–3910. doi: 10.1128/jvi.62.10.3907-3910.1988. [DOI] [PMC free article] [PubMed] [Google Scholar]
  22. 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]
  23. Murphy B. R., Sotnikov A., Paradiso P. R., Hildreth S. W., Jenson A. B., Baggs R. B., Lawrence L., Zubak J. J., Chanock R. M., Beeler J. A. Immunization of cotton rats with the fusion (F) and large (G) glycoproteins of respiratory syncytial virus (RSV) protects against RSV challenge without potentiating RSV disease. Vaccine. 1989 Dec;7(6):533–540. doi: 10.1016/0264-410x(89)90278-8. [DOI] [PubMed] [Google Scholar]
  24. Olmsted R. A., Buller R. M., Collins P. L., London W. T., Beeler J. A., Prince G. A., Chanock R. M., Murphy B. R. Evaluation in non-human primates of the safety, immunogenicity and efficacy of recombinant vaccinia viruses expressing the F or G glycoprotein of respiratory syncytial virus. Vaccine. 1988 Dec;6(6):519–524. doi: 10.1016/0264-410x(88)90104-1. [DOI] [PubMed] [Google Scholar]
  25. 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]
  26. Paccaud M. F., Jacquier C. A respiratory syncytial virus of bovine origin. Arch Gesamte Virusforsch. 1970;30(4):327–342. doi: 10.1007/BF01258363. [DOI] [PubMed] [Google Scholar]
  27. Porter D. D., Prince G. A., Hemming V. G., Porter H. G. Pathogenesis of human parainfluenza virus 3 infection in two species of cotton rats: Sigmodon hispidus develops bronchiolitis, while Sigmodon fulviventer develops interstitial pneumonia. J Virol. 1991 Jan;65(1):103–111. doi: 10.1128/jvi.65.1.103-111.1991. [DOI] [PMC free article] [PubMed] [Google Scholar]
  28. 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]
  29. Prince G. A., Jenson A. B., Hemming V. G., Murphy B. R., Walsh E. E., Horswood R. L., Chanock R. M. Enhancement of respiratory syncytial virus pulmonary pathology in cotton rats by prior intramuscular inoculation of formalin-inactiva ted virus. J Virol. 1986 Mar;57(3):721–728. doi: 10.1128/jvi.57.3.721-728.1986. [DOI] [PMC free article] [PubMed] [Google Scholar]
  30. 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]
  31. Prince G. A., Potash L., Horswood R. L., Camargo E., Suffin S. C., Johnson R. A., Chanock R. M. Intramuscular inoculation of live respiratory syncytial virus induces immunity in cotton rats. Infect Immun. 1979 Mar;23(3):723–728. doi: 10.1128/iai.23.3.723-728.1979. [DOI] [PMC free article] [PubMed] [Google Scholar]
  32. 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]
  33. Thomas L. H., Stott E. J., Collins A. P., Crouch S., Jebbett J. Infection of gnotobiotic calves with a bovine and human isolate of respiratory syncytial virus. Modification of the response by dexamethasone. Arch Virol. 1984;79(1-2):67–77. doi: 10.1007/BF01314304. [DOI] [PubMed] [Google Scholar]
  34. Trudel M., Nadon F., Séguin C., Binz H. Protection of BALB/c mice from respiratory syncytial virus infection by immunization with a synthetic peptide derived from the G glycoprotein. Virology. 1991 Dec;185(2):749–757. doi: 10.1016/0042-6822(91)90546-n. [DOI] [PubMed] [Google Scholar]
  35. Trudel M., Nadon F., Séguin C., Brault S., Lusignan Y., Lemieux S. Initiation of cytotoxic T-cell response and protection of Balb/c mice by vaccination with an experimental ISCOMs respiratory syncytial virus subunit vaccine. Vaccine. 1992;10(2):107–112. doi: 10.1016/0264-410x(92)90026-g. [DOI] [PubMed] [Google Scholar]
  36. Trudel M., Nadon F., Séguin C., Simard C., Lussier G. Experimental polyvalent ISCOMs subunit vaccine induces antibodies that neutralize human and bovine respiratory syncytial virus. Vaccine. 1989 Feb;7(1):12–16. doi: 10.1016/0264-410x(89)90004-2. [DOI] [PubMed] [Google Scholar]
  37. 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]
  38. Walsh E. E., Hall C. B., Schlesinger J. J., Brandriss M. W., Hildreth S., Paradiso P. Comparison of antigenic sites of subtype-specific respiratory syncytial virus attachment proteins. J Gen Virol. 1989 Nov;70(Pt 11):2953–2961. doi: 10.1099/0022-1317-70-11-2953. [DOI] [PubMed] [Google Scholar]
  39. Wathen M. W., Brideau R. J., Thomsen D. R. Immunization of cotton rats with the human respiratory syncytial virus F glycoprotein produced using a baculovirus vector. J Infect Dis. 1989 Feb;159(2):255–264. doi: 10.1093/infdis/159.2.255. [DOI] [PubMed] [Google Scholar]
  40. Wathen M. W., Kakuk T. J., Brideau R. J., Hausknecht E. C., Cole S. L., Zaya R. M. Vaccination of cotton rats with a chimeric FG glycoprotein of human respiratory syncytial virus induces minimal pulmonary pathology on challenge. J Infect Dis. 1991 Mar;163(3):477–482. doi: 10.1093/infdis/163.3.477. [DOI] [PubMed] [Google Scholar]
  41. 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]
  42. Wright P. F., Belshe R. B., Kim H. W., Van Voris L. P., Chanock R. M. Administration of a highly attenuated, live respiratory syncytial virus vaccine to adults and children. Infect Immun. 1982 Jul;37(1):397–400. doi: 10.1128/iai.37.1.397-400.1982. [DOI] [PMC free article] [PubMed] [Google Scholar]

Articles from Journal of Virology are provided here courtesy of American Society for Microbiology (ASM)

RESOURCES