Utilization of a model vaccination system to evaluate the immunostimulatory characteristics of LicKM, a novel carrier molecule
Date
2015
Authors
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Publisher
University of Delaware
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. This project investigates the bacterial carrier molecule from Clostridium thermocellum a modified Lichenase (LicKM), to determine if it posses adjuvant-like capabilities. This thermostable enzyme contains a catalytic domain loop structure separating it into two regions; an N-terminal and C-terminal region (Musiychuk, 2007). Target protein sequences are expressed as either N or C terminal fusions; LicKM may contain a single or double fusions (Musiychuk, 2007). We hypothesize, based upon preliminary results that this molecule serves a dual purpose, as a carrier of dominant epitopes for presentation to antigen presenting cells during vaccination and also as an adjuvant enhancing immunity. Here, we investigated expression of common dendritic cell (DC) markers in the presence of LicKM. Next, the ability of LicKM to suppress the immune response in the presence of a potent activator was assessed. To start to elucidate the potential mechanism of action of LicKM, the interaction of host immune cells with the carrier protein was analyzed. Finally, the humoral immune response following vaccination with LicKM fused target antigens was analyzed. The ultimate goal of this proposal is to demonstrate if LicKM possesses novel adjuvant properties responsible for the development of enhanced cell-mediated responses.