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Journal of Clinical Microbiology logoLink to Journal of Clinical Microbiology
. 1986 Aug;24(2):197–202. doi: 10.1128/jcm.24.2.197-202.1986

Dissociation between serum neutralizing and glycoprotein antibody responses of infants and children who received inactivated respiratory syncytial virus vaccine.

B R Murphy, G A Prince, E E Walsh, H W Kim, R H Parrott, V G Hemming, W J Rodriguez, R M Chanock
PMCID: PMC268874  PMID: 3755730

Abstract

The serum antibody response of infants and children immunized with Formalin-inactivated respiratory syncytial virus (RSV) vaccine 20 years ago was determined by using an enzyme-linked immunosorbent assay specific for the RSV fusion (F) and large (G) glycoproteins and a neutralization assay. Twenty-one young infants (2 to 6 months of age) developed a high titer of antibodies to the F glycoprotein but had a poor response to the G glycoprotein. Fifteen older individuals (7 to 40 months of age) developed titers of F and G antibodies comparable to those in children who were infected with RSV. However, both immunized infants and children developed a lower level of neutralizing antibodies than did individuals of comparable age with natural RSV infections. Thus, the treatment of RSV with Formalin appears to have altered the epitopes of the F or G glycoproteins or both that stimulate neutralizing antibodies, with the result that the immune response consisted largely of "nonfunctional" (i.e., nonneutralizing) antibodies. Subsequent natural infection of the vaccinees with wild-type RSV resulted in enhanced pulmonary disease. Despite this potentiation of illness, the infected vaccinees developed relatively poor G, F, and neutralizing antibody responses. Any or all of three factors may have contributed to the enhancement of disease in the RSV-infected vaccinees. First, nonfunctional antibodies induced by the inactivated RSV vaccine may have participated in a pulmonary Arthus reaction during RSV infection. Second, the poor antibody response of infants to the G glycoprotein present in the Formalin-inactivated vaccine may have been inadequate to provide effective resistance to subsequent wild-type virus infection. Third, the relatively reduced neutralizing antibody response of the infant vaccinees to wild-type RSV infection may have contributed to their enhanced disease by delaying the clearance of virus from their lungs.

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Selected References

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

  1. Bellanti J. A. Biologic significance of the secretory A immunoglobulins. Pediatrics. 1971 Nov;48(5):715–729. [PubMed] [Google Scholar]
  2. 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]
  3. 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]
  4. 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]
  5. Kim H. W., Arrobio J. O., Brandt C. D., Jeffries B. C., Pyles G., Reid J. L., Chanock R. M., Parrott R. H. Epidemiology of respiratory syncytial virus infection in Washington, D.C. I. Importance of the virus in different respiratory tract disease syndromes and temporal distribution of infection. Am J Epidemiol. 1973 Sep;98(3):216–225. doi: 10.1093/oxfordjournals.aje.a121550. [DOI] [PubMed] [Google Scholar]
  6. 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]
  7. Kim H. W., Leikin S. L., Arrobio J., Brandt C. D., Chanock R. M., Parrott R. H. Cell-mediated immunity to respiratory syncytial virus induced by inactivated vaccine or by infection. Pediatr Res. 1976 Jan;10(1):75–78. doi: 10.1203/00006450-197601000-00015. [DOI] [PubMed] [Google Scholar]
  8. Merz D. C., Scheid A., Choppin P. W. Importance of antibodies to the fusion glycoprotein of paramyxoviruses in the prevention of spread of infection. J Exp Med. 1980 Feb 1;151(2):275–288. doi: 10.1084/jem.151.2.275. [DOI] [PMC free article] [PubMed] [Google Scholar]
  9. Mills J., 5th, Van Kirk J. E., Wright P. F., Chanock R. M. Experimental respiratory syncytial virus infection of adults. Possible mechanisms of resistance to infection and illness. J Immunol. 1971 Jul;107(1):123–130. [PubMed] [Google Scholar]
  10. Murphy B. R., Graham B. S., Prince G. A., Walsh E. E., Chanock R. M., Karzon D. T., Wright P. F. Serum and nasal-wash immunoglobulin G and A antibody response of infants and children to respiratory syncytial virus F and G glycoproteins following primary infection. J Clin Microbiol. 1986 Jun;23(6):1009–1014. doi: 10.1128/jcm.23.6.1009-1014.1986. [DOI] [PMC free article] [PubMed] [Google Scholar]
  11. Norrby E., Enders-Ruckle G., Meulen V. Differences in the appearance of antibodies to structural components of measles virus after immunization with inactivated and live virus. J Infect Dis. 1975 Sep;132(3):262–269. doi: 10.1093/infdis/132.3.262. [DOI] [PubMed] [Google Scholar]
  12. Norrby E., Penttinen K. Differences in antibodies to the surface components of mumps virus after immunization with formalin-inactivated and live vaccines. J Infect Dis. 1978 Nov;138(5):672–676. doi: 10.1093/infdis/138.5.672. [DOI] [PubMed] [Google Scholar]
  13. Orvell C., Norrby E. Immunologic properties of purified Sendai virus glycoproteins. J Immunol. 1977 Dec;119(6):1882–1887. [PubMed] [Google Scholar]
  14. 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]
  15. 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]
  16. RAUH L. W., SCHMIDT R. MEASLES IMMUNIZATION WITH KILLED VIRUS VACCINE. SERUM ANTIBODY TITERS AND EXPERIENCE WITH EXPOSURE TO MEASLES EPIDEMIC. Am J Dis Child. 1965 Mar;109:232–237. doi: 10.1001/archpedi.1965.02090020234007. [DOI] [PubMed] [Google Scholar]
  17. 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]
  18. 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]
  19. 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]
  20. 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]

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