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.
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.
Murphy
B R
BR
Laboratory of Infectious Diseases, National Institutes of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD 20892.
Sotnikov
A V
AV
Lawrence
L A
LA
Banks
S M
SM
Prince
G A
GA
D000818:Animals; D000956:Antigens, Viral / Q000276:immunology*; D001980:Bronchi / Q000473:pathology; D004797:Enzyme-Linked Immunosorbent Assay; D005557:Formaldehyde / Q000494:pharmacology; D015707:HN Protein; D011650:Pulmonary Alveoli / Q000473:pathology; D012136:Respiratory Syncytial Viruses / Q000276:immunology* / Q000302:isolation & purification; D010253:Respirovirus Infections / Q000276:immunology*; D016205:Sigmodontinae; D013997:Time Factors; D015164:Vaccines, Inactivated / Q000276:immunology*; D014759:Viral Envelope Proteins; D014764:Viral Proteins; D014765:Viral Vaccines / Q000302:isolation & purification
D000956:Antigens, Viral; D015707:HN Protein; D015164:Vaccines, Inactivated; D014759:Viral Envelope Proteins; D014764:Viral Proteins; D014765:Viral Vaccines; C116204:attachment protein G; D005557:Formaldehyde