Vaccine-elicited CD8+T cells protect against respiratory syncytial virus strain A2-line19F-induced pathogenesis in BALB/c mice

Sujin Lee, Kate L. Stokes, Michael G. Currier, Kaori Sakamoto, Nicholas W. Lukacs, Esteban Celis, Martin L. Moore

Research output: Contribution to journalArticle

34 Scopus citations

Abstract

CD8+ T cells may contribute to vaccines for respiratory syncytial virus (RSV). Compared to CD8+ T cells responding to RSV infection, vaccine-elicited anti-RSV CD8+ T cells are less well defined. We used a peptide vaccine to test the hypothesis that vaccine-elicited RSV-specific CD8+ T cells are protective against RSV pathogenesis. BALB/c mice were treated with a mixture (previously termed TriVax) of an M282-90 peptide representing an immunodominant CD8 epitope, the Toll-like receptor (TLR) agonist poly(I·C), and a costimulatory anti-CD40 antibody. TriVax vaccination induced potent effector anti-RSV CD8+ cytotoxic T lymphocytes (CTL). Mice were challenged with RSV strain A2-line19F, a model of RSV pathogenesis leading to airway mucin expression. Mice were protected against RSV infection and against RSV-induced airway mucin expression and cellular lung inflammation when challenged 6 days after vaccination. Compared to A2-line19F infection alone, TriVax vaccination followed by challenge resulted in effector CD8+ T cells with greater cytokine expression and the more rapid appearance of RSV-specific CD8+ T cells in the lung. When challenged 42 days after TriVax vaccination, memory CD8+ T cells were elicited with RSV-specific tetramer responses equivalent to TriVax-induced effector CD8+ T cells. These memory CD8+ T cells had lower cytokine expression than effector CD8+ T cells, and protection against A2-line19F was partial during the memory phase. We found that vaccine-elicited effector anti-RSV CD8+ T cells protected mice against RSV infection and pathogenesis, and waning protection correlated with reduced CD8+ T cell cytokine expression.

Original languageEnglish (US)
Pages (from-to)13016-13024
Number of pages9
JournalJournal of Virology
Volume86
Issue number23
DOIs
StatePublished - Dec 1 2012
Externally publishedYes

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ASJC Scopus subject areas

  • Microbiology
  • Immunology
  • Insect Science
  • Virology

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