CD8 T cells inhibit respiratory syncytial virus (RSV) vaccine-enhanced disease

J Immunol. 2007 Oct 15;179(8):5415-24. doi: 10.4049/jimmunol.179.8.5415.

Abstract

Vaccination of children with a formalin-inactivated (FI) respiratory syncytial virus (RSV) vaccine led to exacerbated disease including pulmonary eosinophilia following a natural RSV infection. Immunization of BALB/c mice with FI-RSV or a recombinant vaccinia virus (vv) expressing the RSV attachment (G) protein (vvG) results in a pulmonary Th2 response and eosinophilia after RSV challenge that closely mimics the RSV vaccine-enhanced disease observed in humans. The underlying causes of RSV vaccine-enhanced disease remain poorly understood. We demonstrate here that RSV M2-specific CD8 T cells reduce the Th2-mediated pathology induced by vvG-immunization and RSV challenge in an IFN-gamma-independent manner. We also demonstrate that FI-RSV immunization does not induce a measurable RSV-specific CD8 T cell response and that priming FI-RSV-immunized mice for a potent memory RSV-specific CD8 T cell response abrogates pulmonary eosinophilia after subsequent RSV challenge. Our results suggest that the failure of the FI-RSV vaccine to induce a CD8 T cell response may have contributed to the development of pulmonary eosinophilia and augmented disease that occurred in vaccinated individuals.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • CD8-Positive T-Lymphocytes / immunology*
  • CD8-Positive T-Lymphocytes / virology
  • Epitopes, T-Lymphocyte / immunology
  • Female
  • Immunologic Memory
  • Immunosuppression Therapy*
  • Kinetics
  • Lymphocyte Depletion
  • Mice
  • Mice, Inbred BALB C
  • Pulmonary Eosinophilia / immunology
  • Pulmonary Eosinophilia / prevention & control
  • Pulmonary Eosinophilia / virology
  • Respiratory Syncytial Virus Infections / immunology
  • Respiratory Syncytial Virus Infections / prevention & control*
  • Respiratory Syncytial Virus Infections / virology
  • Respiratory Syncytial Virus Vaccines / immunology*
  • Respiratory Syncytial Viruses / immunology*
  • Th2 Cells / immunology
  • Th2 Cells / pathology

Substances

  • Epitopes, T-Lymphocyte
  • Respiratory Syncytial Virus Vaccines