Respiratory syncytial virus (RSV) causes significant morbidity and mortality in children and the elderly. There is no RSV vaccine in use. One of the major obstacles to RSV vaccine development is that RSV re-infects humans throughout life due to lack of durable protective immunity. We hypothesized that maintenance of robust and long-lasting memory CD8 T cells would be the key factor to prevent RSV infection. Recently, we generated a TriVax vaccination approach (peptide, polyI:C, and agonistic α-CD40 mAb). TriVax vaccination in mice completely protected against RSV infection at the effector phase, but protection against RSV was partial during the memory phase. 41BB (CD137) plays a key role in the survival of memory CD8 T cells. To determine whether co-administration of α-41BB in conjunction with TriVax could improve the maintenance of RSV-specific CD8 T cells at memory phase, we administered α-41BB (clone 3H3) or control IgG on the day of TriVax vaccination, and again 2 days later. Data indicated that co-administration of α-41BB and TriVax maintained 30% RSV-specific CD8 T cells until day 35 after the boost. Administration of TriVax+α-41BB followed by challenge using RSV rA2-line19F strain resulted in increased CD8 T cell cytokine expression and protection against RSV infection at memory phase as compared to TriVax+isotype control. Collectively, these data suggest that 41BB may be a promising candidate for the induction of long-lasting RSV-specific memory CD8 T cell immunity.
- Copyright © 2013 by The American Association of Immunologists, Inc.