Evaluating the immunostimulatory characteristics of LicKM, a novel carrier protein.

Abstract

Abstract The key objective of vaccination is the induction of an effective pathogen-specific immune response that leads to protection against infection and/or disease caused by that pathogen. New vaccine technologies have resulted in second-generation recombinant vaccines containing highly purified antigens with improved tolerability and safety profiles. Unfortunately, the immune responses they induce are suboptimal without the help of adjuvants. Here, utilizing a non-toxic bacterial carrier molecule from Clostridium thermocellum a modified Lichenase (LicKM) and based upon preliminary results we hypothesize, that this serves a dual purpose; as both a mechanism to carrier dominant immunogenic epitopes for presentation to antigen presenting cells during vaccination and as an adjuvant enhancing immunity. This thermostable enzyme contains a catalytic domain loop structure separating it into two regions; an N-terminal and C-terminal region. Target protein sequences are expressed as either N or C terminal fusions; and this molecule, LicKM, may contain a single or double fusion. Currently, we are investigating the mechanism by which this molecule enhances the host humoral and cell-mediated response to vaccination. At this time, we have determined that LicKM physically binds to cells associated with the immune response. Additionally, murine vaccination in the presence of LicKM enhances antibody isotype titer production and possibly enhances the cellular responses. Our goal is to understand the immunostimulatory capability of this protein for its possible use to enhance future vaccination protocols.