+ Site Statistics
References:
54,258,434
Abstracts:
29,560,870
PMIDs:
28,072,757
+ Search Articles
+ PDF Full Text Service
How our service works
Request PDF Full Text
+ Follow Us
Follow on Facebook
Follow on Twitter
Follow on LinkedIn
+ Subscribe to Site Feeds
Most Shared
PDF Full Text
+ Translate
+ Recently Requested

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



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 10(7): 475-484



In studies conducted in the 1960s, children previously immunized with a formalin-inactivated respiratory syncytial virus (RSV) vaccine (FI-RSV) developed a greater incidence and severity of pulmonary disease during subsequent natural RSV infection than did controls. It was previously shown that cotton rats immunized with FI-RSV or immunoaffinity-purified fusion (F) glycoprotein developed enhanced pulmonary histopathology following intranasal challenge with RSV. In the present studies, various forms of immunization, including parenteral inoculation of an immunoaffinity-purified F glycoprotein or a chimeric FG glycoprotein produced in insect cells using a baculovirus vector (Bac-FG), intradermal infection with vaccinia-F recombinant (Vac-F) or intranasal infection with an adenovirus-F recombinant (Ad-F) or RSV, were compared for immunogenicity, efficacy and ability to alter the host so that enhanced pulmonary histopathology developed during RSV infection 3 months after immunization. Immunization of cotton rats with F glycoprotein, Bac-FG, Vac-F, Ad-F or infection with RSV induced high levels of ELISA-F antibodies, but the antibodies induced by purified F glycoprotein of Bac-FG had low levels of neutralizing activity. Immunization with Vac-F or Ad-F, or infection with RSV induced a high level of resistance to pulmonary RSV replication, whereas animals immunized with Bac-FG or FI-RSV were only partially protected. Following RSV challenge, animals immunized with purified F glycoprotein or Bac-FG developed the highest levels of bronchiolar and alveolar histopathology, those immunized with FI-RSV had intermediate levels, and those immunized with Vac-F or RSV had histopathology scores at control levels. Ad-F immunized animals had elevated scores of bronchiolar but not alveolar histopathology; however, this finding was not reproducible. Passive transfer of pooled immune sera from animals injected with RSV or Vac-F and Vac-G was highly protective, whereas pooled sera from animals immunized with Bac-FG failed to protect the lungs against RSV challenge. Increased pulmonary histopathology was not observed in the passively immunized animals following RSV challenge, suggesting that the histopathology was mediated by RSV-specific T cells. These data indicate that subunit F glycoprotein or chimeric FG vaccines share with FI-RSV the properties of (i) induction of F antibodies with low neutralizing activity and (ii) enhancement of pulmonary histopathology during subsequent RSV infection. These observations confirm the need for caution in studies involving the administration of RSV subunit vaccines to seronegative humans.

Please choose payment method:






(PDF emailed within 1 workday: $29.90)

Accession: 007165750

Download citation: RISBibTeXText

PMID: 1609551


Related references

Lack of detectable enhanced pulmonary histopathology in cotton rats immunized with purified F glycoprotein of respiratory syncytial virus (RSV) when challenged at 3-6 months after immunization. Vaccine 11(6): 615-618, 1993

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 8(5): 497-502, 1990

Vaccination of cotton rats with a chimeric FG glycoprotein of human respiratory syncytial virus induces minimal pulmonary pathology on challenge. Journal of Infectious Diseases 163(3): 477-482, 1991

Enhanced pulmonary pathology in cotton rats upon challenge after immunization with inactivated parainfluenza virus 3 vaccines. Viral Immunology 13(2): 231-236, 2000

Enhanced pulmonary pathology associated with the use of formalin-inactivated respiratory syncytial virus vaccine in cotton rats is not a unique viral phenomenon. Vaccine. 11(14): 1415-1423, 1993

Induction of systemic and mucosal immune responses in cotton rats immunized with human adenovirus type 5 recombinants expressing the full and truncated forms of bovine herpesvirus type 1 glycoprotein gD. Virology 222(2): 299-309, 1996

Enhanced cellular immune responses to SIV Gag by immunization with influenza and vaccinia virus recombinants. Vaccine 21(17-18): 2097-2106, 2003

Enhanced CD8+ T cell response to HIV-1 env by combined immunization with influenza and vaccinia virus recombinants. Vaccine 17(7-8): 887-892, 1999

Expression of herpes simplex virus glycoprotein D on antigen presenting cells infected with vaccinia recombinants and protective immunity. Bioscience Reports 8(4): 323-334, 1988

Resistance to human respiratory syncytial virus (RSV) infection induced by immunization of cotton rats with a recombinant vaccinia virus expressing the RSV G glycoprotein. Proceedings of the National Academy of Sciences of the United States of America 83(6): 1906-1910, 1986