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

J Virol. 1996 May;70(5):2852-60. doi: 10.1128/JVI.70.5.2852-2860.1996.

Abstract

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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Base Sequence
  • Bronchoalveolar Lavage Fluid / cytology
  • Bronchoalveolar Lavage Fluid / immunology
  • CD4 Lymphocyte Count
  • Cytokines / biosynthesis*
  • DNA Primers
  • Formaldehyde
  • Inflammation
  • Interleukins / biosynthesis*
  • Leukocyte Count
  • Lung / immunology*
  • Lung / pathology
  • Lung / virology
  • Lymphocyte Count
  • Mice
  • Mice, Inbred BALB C
  • Molecular Sequence Data
  • Polymerase Chain Reaction
  • RNA, Messenger / analysis
  • Respiratory Syncytial Virus Infections / immunology*
  • Respiratory Syncytial Virus Infections / pathology
  • Respiratory Syncytial Viruses / immunology*
  • Respiratory Syncytial Viruses / isolation & purification
  • Respiratory Syncytial Viruses / physiology
  • Th2 Cells / immunology*
  • Vaccines, Inactivated*
  • Viral Vaccines*
  • Virus Replication

Substances

  • Cytokines
  • DNA Primers
  • Interleukins
  • RNA, Messenger
  • Vaccines, Inactivated
  • Viral Vaccines
  • Formaldehyde