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.


Formalin-inactivated (FI) RSV, purified F glycoprotein in alum, and RSV infection (intranasal) were compared for their immunogenicity, efficacy, and ability to enhance pulmonary histopathology during RSV infection 3 and 6 months following immunization by the intramuscular route. Purified influenza virus in alum was used as a control immunogen. At 1 month following immunization with one dose of purified F glycoprotein (5 micrograms), cotton rats developed levels of F antibodies (ELISA) higher than the other groups, but these antibodies had the lowest level of neutralizing activity, Little increase in antibody titre was seen following a second dose of FI-RSV or purified F vaccine given at 1 month. Animals that received 5 micrograms F, 0.5 microgram F, or were almost completely resistant to pulmonary RSV infection following challenge at 3 months, but were susceptible by 6 months. Animals immunized with 5 micrograms of purified F glycoprotein developed alveolar and bronchiolar histopathology following RSV challenge at 3 or 6 months which was comparable to that of animals immunized with FI-RSV. These levels significantly exceeded those in animals previously immunized with influenza A virus vaccine which exhibited little histopathology. Animals previously infected with RSV also developed bronchiolar, but not alveolar, histopathology suggesting that the bronchiolar histopathology seen in RSV challenged cotton rats is a normal component of the immune resolution of RSV infection. These results suggest that the immune response of cotton rats to immunoaffinity purified F glycoprotein can result in enhanced bronchiolar and alveolar histopathology following RSV challenge. Thus, caution should be exercised in studies in humans using a purified F glycoprotein subunit vaccine.

Publication types

  • Comparative Study

MeSH terms

  • Animals
  • Antigens, Viral / immunology*
  • Bronchi / pathology
  • Enzyme-Linked Immunosorbent Assay
  • Formaldehyde / pharmacology
  • HN Protein*
  • Pulmonary Alveoli / pathology
  • Respiratory Syncytial Viruses / immunology*
  • Respiratory Syncytial Viruses / isolation & purification
  • Respirovirus Infections / immunology*
  • Sigmodontinae
  • Time Factors
  • Vaccines, Inactivated / immunology*
  • Viral Envelope Proteins
  • Viral Proteins*
  • Viral Vaccines / isolation & purification


  • Antigens, Viral
  • HN Protein
  • Vaccines, Inactivated
  • Viral Envelope Proteins
  • Viral Proteins
  • Viral Vaccines
  • attachment protein G
  • Formaldehyde