title: Vaccine-elicited CD8+ T cells protect against respiratory syncytial virus strain A2-line19F-induced pathogenesis in BALB/c mice.
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 M2(82-90) 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.
authors.affiliation: Department of Pediatrics, Emory University, Atlanta, Georgia, USA.
authors.forename: Sujin
authors.initials: S
authors.lastname: Lee
authors.forename: Kate L
authors.initials: KL
authors.lastname: Stokes
authors.forename: Michael G
authors.initials: MG
authors.lastname: Currier
authors.forename: Kaori
authors.initials: K
authors.lastname: Sakamoto
authors.forename: Nicholas W
authors.initials: NW
authors.lastname: Lukacs
authors.forename: Esteban
authors.initials: E
authors.lastname: Celis
authors.forename: Martin L
authors.initials: ML
authors.lastname: Moore
mesh_terms: D000704:Analysis of Variance; D000818:Animals; D000914:Antibodies, Viral / Q000494:pharmacology; D018414:CD8-Positive T-Lymphocytes / Q000187:drug effects / Q000276:immunology*; D005260:Female; D005434:Flow Cytometry; D006652:Histological Techniques; D008168:Lung / Q000276:immunology* / Q000821:virology; D051379:Mice; D008807:Mice, Inbred BALB C; D011070:Poly I-C / Q000494:pharmacology; D018357:Respiratory Syncytial Virus Infections / Q000276:immunology / Q000503:physiopathology / Q000517:prevention & control*; D051193:Toll-Like Receptors / Q000819:agonists; D014611:Vaccination; D014765:Viral Vaccines / Q000276:immunology / Q000494:pharmacology*
chemical_list: D000914:Antibodies, Viral; D051193:Toll-Like Receptors; D014765:Viral Vaccines; D011070:Poly I-C