Gene expression differences in lungs of mice during secondary immune responses to respiratory syncytial virus infection.
Vaccine-induced immunity has been shown to alter the course of a respiratory syncytial virus (RSV) infection both in murine models and in humans. To elucidate which mechanisms underlie the effect of vaccine-induced immunity on the course of RSV infection, transcription profiles in the lungs of RSV-infected mice were examined by microarray analysis. Three models were used: RSV reinfection as a model for natural immunity, RSV challenge after formalin-inactivated RSV vaccination as a model for vaccine-enhanced disease, and RSV challenge following vaccination with recombinant RSV virus lacking the G gene (DeltaG-RSV) as a model for vaccine-induced immunity. Gene transcription profiles, histopathology, and viral loads were analyzed at 1, 2, and 5 days after RSV challenge. On the first 2 days after challenge, all mice displayed an expression pattern in the lung similar of that found in primary infection, showing a strong innate immune response. On day 5 after RSV reinfection or after challenge following DeltaG-RSV vaccination, the innate immune response was waning. In contrast, in mice with vaccine-enhanced disease, the innate immune response 5 days after RSV challenge was still present even though viral replication was diminished. In addition, only in this group was Th2 gene expression induced. These findings support a hypothesis that vaccine-enhanced disease is mediated by prolonged innate immune responses and Th2 polarization in the absence of viral replication.
Schuurhof
Annemieke
A
Laboratory for Health Protection Research, National Institute for Public Health and the Environment, Bilthoven, The Netherlands.
Bont
Louis
L
Pennings
Jeroen L A
JL
Hodemaekers
Hennie M
HM
Wester
Piet W
PW
Buisman
Annemarie
A
de Rond
Lia C G H
LC
Widjojoatmodjo
Myra N
MN
Luytjes
Willem
W
Kimpen
Jan L L
JL
Janssen
Riny
R
D000818:Animals; D005260:Female; D015870:Gene Expression; D020869:Gene Expression Profiling; D006651:Histocytochemistry; D008168:Lung / Q000276:immunology* / Q000473:pathology / Q000821:virology; D051379:Mice; D008807:Mice, Inbred BALB C; D020411:Oligonucleotide Array Sequence Analysis; D018357:Respiratory Syncytial Virus Infections / Q000276:immunology* / Q000473:pathology / Q000821:virology; D022261:Respiratory Syncytial Virus Vaccines / Q000276:immunology*; D012136:Respiratory Syncytial Viruses / Q000276:immunology*; D018418:Th2 Cells / Q000276:immunology; D013997:Time Factors; D019562:Viral Load
D022261:Respiratory Syncytial Virus Vaccines