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Understanding respiratory syncytial virus (RSV) vaccine-enhanced disease

Immunologic Research volume 39, pages 225–239 (2007)Cite this article

Abstract

Respiratory syncytial virus (RSV) is the most common cause of lower respiratory tract infection in infants and children worldwide. In addition, RSV causes serious disease in elderly and immune compromised individuals. RSV infection of children previously immunized with a formalin-inactivated (FI)-RSV vaccine is associated with enhanced disease and pulmonary eosinophilia that is believed to be due to an exaggerated memory Th2 response. As a consequence, there is currently no licensed RSV vaccine and detailed studies directed towards prevention of vaccine-associated disease are a critical first step in the development of a safe and effective vaccine. The BALB/c mouse model of RSV infection faithfully mimics the human respiratory disease. Mice previously immunized with either FI-RSV or a recombinant vaccinia virus (vv) that expresses the attachment (G) glycoprotein exhibit extensive lung inflammation and injury, pulmonary eosinophilia, and enhanced disease following challenge RSV infection. CD4 T cells secreting Th2 cytokines are necessary for this response because their depletion eliminates eosinophilia. Intriguing recent studies have demonstrated that RSV-specific CD8 T cells can inhibit Th2-mediated pulmonary eosinophilia in vvG-primed mice by as yet unknown mechanisms. Information gained from the animal models will provide important information and novel approaches for the rational design of a safe and efficacious RSV vaccine.

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Affiliations

  1. Interdisciplinary Graduate Program in Immunology, University of Iowa, 3-532 Bowen Science Building, 51 Newton Road, Iowa City, IA, 52242, USA

    Elaine M. Castilow & Steven M. Varga

  2. Department of Microbiology, University of Iowa, 3-532 Bowen Science Building, 51 Newton Road, Iowa City, IA, 52242, USA

    Matthew R. Olson & Steven M. Varga

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  1. Elaine M. Castilow
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  2. Matthew R. Olson
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  3. Steven M. Varga
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Correspondence to Steven M. Varga.

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Elaine M. Castilow and Matthew R. Olson contributed equally to the preparation of this manuscript.

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Castilow, E.M., Olson, M.R. & Varga, S.M. Understanding respiratory syncytial virus (RSV) vaccine-enhanced disease. Immunol Res 39, 225–239 (2007). https://doi.org/10.1007/s12026-007-0071-6

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Keywords

  • RSV
  • T cell
  • Th2 cell
  • Eosinophils
  • Vaccine
  • Immunopathology