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Targeting CD137 Enhances Vaccine-Elicited Anti-Respiratory Syncytial Virus CD8+ T Cell Responses in Aged Mice.
- Source :
-
Journal of Immunology . 1/1/2014, Vol. 192 Issue 1, p293-299. 7p. - Publication Year :
- 2014
-
Abstract
- Respiratory syncytial virus (RSV) causes significant morbidity and mortality in children and the elderly. No vaccines for RSV are in use. Because of immunosenescence, the immunologic requirements for a successful RSV vaccine in the elderly might differ from a RSV vaccine for young children. Using an aged mouse model of RSV pathogenesis, we found that aged mice had impaired Agspecific CD8+ T cell responses and delayed RSV clearance compared with young mice. To study vaccine-elicited RSV-specific CD8+ T cells in aged mice, we used a peptide vaccine approach. TriVax is a commixture of a peptide representing immunodominant RSV CD8+ T cell epitope M282-90, a TLR agonist (polyinosinic-polycytidylic acid), and a costimulatory anti-CD40 Ab. TriVax vaccination generated robust, polyfunctional, and protective CD8+ T cell responses in young BALB/c mice, but not in 18-mo-old (aged) BALB/c mice. We hypothesized that treatment of aged mice with agonistic anti-CD137 (41BB) mAb will partially restore T cell responses and TriVax efficacy in aged mice. We immunized 18-mo-old BALB/c mice twice with TriVax + anti-41BB mAb or TriVax + isotype control Ab. Coadministration of anti-41BB mAb with TriVax enhanced RSV-specific CD8+ T cell responses and TriVax efficacy in challenge experiments. Triggering the 41BB costimulatory pathway may be a strategy for enhancing T cell responses to vaccines in the elderly. [ABSTRACT FROM AUTHOR]
Details
- Language :
- English
- ISSN :
- 00221767
- Volume :
- 192
- Issue :
- 1
- Database :
- Academic Search Index
- Journal :
- Journal of Immunology
- Publication Type :
- Academic Journal
- Accession number :
- 103537806
- Full Text :
- https://doi.org/10.4049/jimmunol.1300453