Many of the vaccines currently used today contain alum, leading to the production of neutralizing antibodies, but not good CD8 T cell responses.  Vaccines that induce good cellular immunity are needed for chronic diseases such as cancer.  Our lab has recently shown that the combined stimuli of a Toll-like receptor (TLR) agonist and agonistic anti-CD40 antibody with an antigen synergizes to induce the generation of a CD8 T cell response comparable to that seen during an infection.  This is in contrast to immunization with either of these agonists by themselves where only minimal T cell responses are generated.  We have found that the CD8 T cell response generated by this vaccine is dependent on the expression of CD70 on dendritic cells and is variably dependent on Type I Interferon (IFN).  The degree to which the CD8 T cell response depends on Type I IFN directly correlates with the amount of Type I IFN induced by the TLR agonist used for immunization.

 

My focus in the lab is to determine the role for Type I IFN during immunization with Type I IFN inducing TLR agonists.  More specifically, I am looking at whether Type I IFN is enhancing CD8 T cell responses by acting on the dendritic cell to upregulate costimulatory molecules or acting directly on the T cell.  Determining how our vaccination method works to enhance CD8 T cell responses could potentially lead to the generation of vaccines for diseases where cellular immune responses are most necessary for immunity.

 

Keystone Minority Travel Scholarship

 

Sanchez PJ, McWilliams JA, Haluszczak C, Yagita H, Kedl RM. Combined TLR/CD40 stimulation mediates potent cellular immunity by regulating dendritic cell expression of CD70 in vivo. J Immunol. 2007 Feb 1;178(3):1564-72.

 

McMahan RH, McWilliams JA, Jordan KR, Dow SW, Wilson DB, Slansky JE. Relating TCR-peptide-MHC affinity to immunogenicity for the design of tumor vaccines. J Clin Invest. 2006 Sep;116(9):2543-51.

 

McWilliams JA, McGurran SM, Dow SW, Slansky JE, Kedl RM. A modified tyrosinase-related protein 2 epitope generates high-affinity tumor-specific T cells but does not mediate therapeutic efficacy in an intradermal tumor model. J Immunol. 2006 Jul 1;177(1):155-61.