Vaccine-elicited CD8+ T cells protect against respiratory syncytial virus-induced lung airway obstruction (113.8)

Abstract

Abstract Respiratory syncytial virus (RSV) is the most important pathogen for lower respiratory tract illness in infants. CD8+ T cells clear RSV and may contribute to future RSV vaccines. RSV itself inhibits CD8+ T cell responses. Compared to CD8+ T cells responding to RSV infection, vaccine-elicited anti-RSV CD8+ T cells are less well studied, and mechanisms for achieving optimally functional anti-RSV CD8+ T cells are not defined. We developed a novel RSV vaccination strategy using combined toll-like receptor (TLR) and CD40 stimulation in BALB/c mice as a model for studying antigen-defined RSV-specific CD8+ T cells. Vaccination of mice with TriVax, a mixture of a M2 82-90 peptide representing an immunodominant RSV CD8 epitope, the TLR agonist poly (I:C), and a costimulatory anti-CD40 antibody resulted in robust, functional CD8+ CTL responses. Using a mucus-inducing RSV challenge strain (rA2-line19F), we demonstrate that TriVax vaccination protected against RSV infection and RSV-induced airway mucus expression, mechanical airway obstruction, and cellular lung inflammation. Compared to RSV challenge alone, TriVax vaccination followed by challenge resulted in increased CD8+ T cell cytokine expression and the rapid appearance of RSV-specific CD8+ T cells in the lung. Despite a large number of cytokine expressing and virus-specific CD8+ T cells in the lung, TriVax vaccination did not cause immunopathology. High-quality vaccine-elicited anti-RSV CD8+ T cells were protective in the lung.