Immunostimulatory adjuvant molecules and antibody recruiting molecule-containing lipopeptide vaccines

Project ID:  D2017-06 Background Protein conjugate vaccines have limitations due to the innate immunogenicity of carrier proteins that can suppress the response against associated antigens. Thus, the development of fully synthetic vaccines have been under intense investigation in the last decade in immunotherapy. A typical fully synthetic vaccine includes B-cell epitopes, cytotoxic T-cell epitopes, helper T-cell epitopes, and an immuno-adjuvant to boost the immune response. There is rapidly expanding interest in the synthesis of custom vaccine epitopes related to virial, bacterial, and cancer antigens. However, a simple approach to enhancing the immune response by combining these antigens with the immunostimulatory adjuvant molecules is lacking. Furthermore, weak immunogens, such as carbohydrate antigens may need additional stimulation to afford robust B and T-cell responses.  Invention DescriptionResearchers at The University of Toledo have developed a unique immunostimulatory adjuvant molecule composition comprised of a modified TLR2 ligand that can be combined with any azide-containing antigen to form TLR2 ligand lipidated antigen compositions.  Additionally, the lipidated peptide or glycopeptide antigen optionally incorporates an antibody recruitment molecule (ARM). The ARM can enhance the immune response through complexation with natural antibodies found in humans. The compositions of the vaccine are more readily assembled than known vaccine components. Furthermore, covalent combination of a lipid antigen and an ARM ensures co-localization of all components.  Specific compositions covering tumor antigens and type I diabetes disease modifying antigens are included.   Applications•       The invention can be applied to the development of anti-viral, anti-bacterial and anti-tumor vaccines as well as vaccines which may lead to the suppression of autoimmune disordersAdvantages•       The compositions of the vaccine are more readily assembled than known vaccine compositions, incorporating a xenoantigen as part of a second molecule or component is optional•       Covalent combination of a lipid-based immunostimulatory adjuvant molecules, antigen and optionally an ARM ensures colocalization of all components•       Endogenous natural antibodies against ARMs can be used to improve uptake of antigen, enhance cross-presentation for cytotoxic T cell generation, or can be used to lower the dose of antigens in the vaccine IP Status:       PCT Patent Pending Publications:       Karmakar P, et al., Synthesis of a liposomal MUC1 glycopeptide-based immunotherapeutic and evaluation of the effect of I-Rhamnose targeting on cellular immune responses. Bioconjugate Chemistry, 2016, 110-120

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