title: The combined molecular adjuvant CASAC enhances the CD8+ T cell response to a tumor-associated self-antigen in aged, immunosenescent mice.
abstract: BACKGROUND
  Ineffective induction of T cell mediated immunity in older individuals remains a persistent challenge for vaccine development. Thus, there is a need for more efficient and sophisticated adjuvants that will complement novel vaccine strategies for the elderly. To this end, we have investigated a previously optimized, combined molecular adjuvant, CASAC (Combined Adjuvant for Synergistic Activation of Cellular immunity), incorporating two complementary Toll-like receptor agonists, CpG and polyI:C, a class-II epitope, and interferon (IFN)-γ in aged mice.
  
  
  RESULTS
  In aged mice with typical features of immunosenescence, antigen specific CD8+ T cell responses were stimulated after serial vaccinations with CASAC or Complete/Incomplete Freund's Adjuvant (CFA/IFA) and a class I epitope, deriving either from ovalbumin (SIINFEKL, SIL) or the melanoma-associated self-antigen, tyrosinase-related protein-2 (SVYDFFVWL, SVL). Pentamer analysis revealed that aged, CASAC/SIL-vaccinated animals had substantially higher frequencies of H-2K(b)/SIL-specific CD8+ T cells compared to the CFA/IFA-vaccinated groups. Similarly, higher frequencies of H-2K(b)/SVL-pentamer+ and IFN-γ+ CD8+ T cells were detected in the aged, CASAC + SVL-vaccinated mice than in their CFA/IFA-vaccinated counterparts. In both antigen settings, CASAC promoted significantly better functional CD8+ T cell activity.
  
  
  CONCLUSIONS
  These studies demonstrate that functional CD8+ T cells, specific for both foreign and tumour-associated self-antigens, can be effectively induced in aged immunosenescent mice using the novel multi-factorial adjuvant CASAC.
authors.affiliation: Department of Haematological Medicine, King's College London, Rayne Institute, London, UK.|Institute for Research in Molecular Medicine, Universiti Sains Malaysia, George town, Malaysia.
authors.forename: Gee Jun
authors.initials: GJ
authors.lastname: Tye
authors.affiliation: Department of Haematological Medicine, King's College London, Rayne Institute, London, UK.
authors.forename: Kyriaki
authors.initials: K
authors.lastname: Ioannou
authors.affiliation: Department of Haematological Medicine, King's College London, Rayne Institute, London, UK.
authors.forename: Eunice
authors.initials: E
authors.lastname: Amofah
authors.affiliation: Department of Haematological Medicine, King's College London, Rayne Institute, London, UK.
authors.forename: Ruby
authors.initials: R
authors.lastname: Quartey-Papafio
authors.affiliation: Department of Haematological Medicine, King's College London, Rayne Institute, London, UK.
authors.forename: Samantha J
authors.initials: SJ
authors.lastname: Westrop
authors.affiliation: Department of Haematological Medicine, King's College London, Rayne Institute, London, UK.
authors.forename: Pramila
authors.initials: P
authors.lastname: Krishnamurthy
authors.affiliation: Medical Research Council and Asthma UK Centre in Allergic Mechanisms of Asthma, King's College London, Guy's Hospital, London, UK.
authors.forename: Alistair
authors.initials: A
authors.lastname: Noble
authors.affiliation: Division of Transplant and Mucosal Cell Biology, King's College London, London, UK.
authors.forename: Phillip M
authors.initials: PM
authors.lastname: Harrison
authors.affiliation: Department of Medicine, University of California, San Francisco School of Medicine, San Francisco, USA.
authors.forename: Karin M L
authors.initials: KML
authors.lastname: Gaensler
authors.affiliation: Department of Haematological Medicine, King's College London, Rayne Institute, London, UK.
authors.forename: Linda D
authors.initials: LD
authors.lastname: Barber
authors.affiliation: Department of Haematological Medicine, King's College London, Rayne Institute, London, UK.
authors.forename: Farzin
authors.initials: F
authors.lastname: Farzaneh
keywords: Ageing; Immunosenescence; Immunotherapy; TLR; Vaccine; adjuvant