Respiratory synctial virus infection in BALB/c mice previously immunized with formalin-inactivated virus induces enhanced pulmonary inflammatory response with a predominant Th2-like cytokine pattern.
Vaccination with formalin-inactivated respiratory syncytial virus (FI-RSV) caused excessive disease in infants upon subsequent natural infection with RSV. Recent studies with BALB/c mice have suggested that T cells are important contributors to lung immunopathology during RSV infection. In this study, we investigated vaccine-induced enhanced disease by immunizing BALB/c mice with live RSV intranasally or with FI-RSV intramuscularly. The mice were challenged with RSV 6 weeks later, and the pulmonary inflammatory response was studied by analyzing cells obtained by bronchoalveolar lavage 4 and 8 days after challenge. FI-RSV-immunized mice had an increased number of total cells, granulocytes, eosinophils, and CD4+ cells but a decreased number of CD8+ cells. The immunized mice also had a marked increase in the expression of mRNA for the Th2-type cytokines interleukin-5 (IL-5) and IL-13 as well as some increase in the expression of IL-10 (a Th2-type cytokine) mRNA and some decrease in the expression of IL-12 (a Th1-type cytokine) mRNA. The clear difference in the pulmonary inflammatory response to RSV between FI-RSV- and live-RSV-immunized mice suggests that this model can be used to evaluate the disease-enhancing potential of candidate RSV vaccines and better understand enhanced disease.
Waris
M E
ME
Division of Viral and Rickettsial Diseases, National Center of Infectious Diseases, Centers for Disease Control and Prevention, Atlanta, Georgia 30333, USA.
Tsou
C
C
Erdman
D D
DD
Zaki
S R
SR
Anderson
L J
LJ
D000818:Animals; D001483:Base Sequence; D001992:Bronchoalveolar Lavage Fluid / Q000166:cytology / Q000276:immunology; D018791:CD4 Lymphocyte Count; D016207:Cytokines / Q000096:biosynthesis*; D017931:DNA Primers; D005557:Formaldehyde; D007249:Inflammation; D007378:Interleukins / Q000096:biosynthesis*; D007958:Leukocyte Count; D008168:Lung / Q000276:immunology* / Q000473:pathology / Q000821:virology; D018655:Lymphocyte Count; D051379:Mice; D008807:Mice, Inbred BALB C; D008969:Molecular Sequence Data; D016133:Polymerase Chain Reaction; D012333:RNA, Messenger / Q000032:analysis; D018357:Respiratory Syncytial Virus Infections / Q000276:immunology* / Q000473:pathology; D012136:Respiratory Syncytial Viruses / Q000276:immunology* / Q000302:isolation & purification / Q000502:physiology; D018418:Th2 Cells / Q000276:immunology*; D015164:Vaccines, Inactivated; D014765:Viral Vaccines; D014779:Virus Replication
D016207:Cytokines; D017931:DNA Primers; D007378:Interleukins; D012333:RNA, Messenger; D015164:Vaccines, Inactivated; D014765:Viral Vaccines; D005557:Formaldehyde