Both immunisation with a formalin-inactivated respiratory syncytial virus (RSV) vaccine and a mock antigen vaccine induce severe lung pathology and a Th2 cytokine profile in RSV-challenged mice.
Respiratory syncytial virus (RSV) is the most important cause of bronchiolitis and pneumonia in infants and young children. Immunopathology may play a role in RSV-induced disease and a severe RSV infection may also be associated with an increased risk of developing asthma. Vaccination with formalin-inactivated RSV (FI-RSV) prior to infection resulted both in human and in the mouse model in extensive lung pathology. In the mouse model, it has been shown that this aggravation of disease was associated with a shift in the balance between Th1 and Th2 cytokines towards a Th2-type response. The aim of the present study was to characterise the immunological and inflammatory responses in BALB/c mice upon RSV infection with or without prior vaccination with aluminium-adjuvanted FI-RSV or control antigens (FI-Mock). As previously reported by others, we also observed that a primary RSV infection in BALB/c mice resulted in a predominant Th1-type cytokine response, which was associated with slight bronchiolitis and alveolitis. FI-RSV vaccination prior to RSV challenge prevented virus replication and was associated with an aggravation of pulmonary histopathology and a shift towards a Th2-type response. Vaccination with FI-Mock did not prevent RSV replication in the lung but resulted in an even more pronounced Th2 response after infection while these mice were not sensitised to specific viral antigens. Thus, viral replication in a Th2 responding animal (induced by aluminium-adjuvanted mock vaccine) appears to boost the Th2 response upon RSV infection.
Boelen
A
A
Research Laboratory for Infectious Diseases, Laboratory for Pathology and Immunology, National Institute of Public Health and the Environment, P.O. Box 1, 3720 BA, Bilthoven, The Netherlands.
Andeweg
A
A
Kwakkel
J
J
Lokhorst
W
W
Bestebroer
T
T
Dormans
J
J
Kimman
T
T
D000818:Animals; D000914:Antibodies, Viral / Q000096:biosynthesis; D002675:Child, Preschool; D016207:Cytokines / Q000096:biosynthesis / Q000235:genetics; D005260:Female; D005557:Formaldehyde; D006801:Humans; D007114:Immunization; D007223:Infant; D007249:Inflammation / Q000209:etiology / Q000473:pathology; D008168:Lung / Q000276:immunology / Q000473:pathology; D051379:Mice; D008807:Mice, Inbred BALB C; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D018357:Respiratory Syncytial Virus Infections / Q000276:immunology* / Q000473:pathology / Q000517:prevention & control*; D012136:Respiratory Syncytial Viruses / Q000276:immunology* / Q000472:pathogenicity* / Q000502:physiology; D018417:Th1 Cells / Q000276:immunology; D018418:Th2 Cells / Q000276:immunology; D015164:Vaccines, Inactivated / Q000008:administration & dosage / Q000633:toxicity; D014765:Viral Vaccines / Q000008:administration & dosage* / Q000633:toxicity*; D014779:Virus Replication
D000914:Antibodies, Viral; D016207:Cytokines; D012333:RNA, Messenger; D015164:Vaccines, Inactivated; D014765:Viral Vaccines; D005557:Formaldehyde