Enhanced Immunogenicity Vaccine Development Platform

Project ID: D2012-14

Background

Extensive research is being carried out globally to develop vaccines for the treatment of different types of infections and diseases. However, improved immunogenicity and efficient delivery of antigens to the antigen producing cells (APCs) via these vaccines is still a challenge. Also, it is very costly and time consuming to develop a particular disease- targeted vaccine from scratch. The disclosed invention is the solution to these limitations and provides a vaccine platform to easily develop improved vaccines of any kind, enclosed in liposome that serves as delivery vehicle of the antigens to APCs.

Invention Description

Scientists at the University of Toledo have developed a platform to develop vaccines for any kind of disease with enhanced immunogenicity via use of conjugatable immunologic adjuvant molecules combined with antibody recruiting molecules (ARMs) to facilitate active antigen update and cross–presentation by antigen presenting cells. Specifically, the scientists have employed this platform for a cancer antigen for the treatment of cancerous cells. These researchers have demonstrated that the immunogenicity of a model antigen, can be increased by incorporation of a lipidated antigen into a liposome which also displays an ARM capable of interacting with natural antibodies (NAs). NAs are abundantly present in human serum allowing for the targeting of antigens to APCs. The scientists also demonstrated a simple method for the synthesis of lipidated peptides. The target lipopeptide antigens contained an N-terminal azido moiety for click conjugation with a synthetic alkynyl derivative of the Toll-like receptor ligand, lipid, and vaccine adjuvant Pam3Cys. The NA ligand, L-rhamnose, was first conjugated with cholesterol using a tetraethylene glycol (TEG) linker. The antigen and NA ligand were associated by formulation into a liposome. The formulated liposomes demonstrated binding with both anti-rhamnose and anti-antigen antibodies. The specific examples pertain to an anti-MUC1 anti-tumor vaccine. However, the technology can be used to enhance the antigenicity of any peptide antigen.

Applications

In the development of prophylactic and therapeutic vaccines to trigger a targeted immune response.

Advantages

The advantages of this technology include:

• Formulated liposome can bind to a wide variety of anti-rhamnose and anti-antigen antibodies
• Improved generation of both antibodies and cytotoxic T-cells through the use of an antibody recruiting molecule (ARM) and natural antibodies
• Separation of antigen from ARM, enabling the technology to serve as a common platform for making different vaccines
• Has shown increased antibody and CD4+/CD8+ T-cell priming in mice
• Cellular material from patients not required, hence manufacturing simplicity
• Inclusion of an adjuvant to further boost the immune response
• Value added APC targeting

IP Status:             Patented US10206988B2, Canada 2,869,691, Europe EP13749613.9

                              Australian patent AU2017201649

Publications:

1. Hossain, M. K.; Vartak, A.; Sucheck, S. J; Wall. K.A. Synthesis and Immunological Evaluation of a Single Molecular Construct MUC1 Vaccine Containing l-Rhamnose Repeating Units Molecules 2020, 25(14), 3137
2. Hossain, M. K.; Vartak, A.; Sucheck, S. J; Wall. K.A.  A liposomal Fc domain conjugated to a cancer vaccine  enhances both humoral and cellular immunity. ACS Omega, 2019, 4, 5204–5208.
3. Development of a Bioconjugate Platform for Modifying the Immune Response of Autoreactive Cytotoxic T Lymphocytes Involved in Type 1 Diabetes. McInerney MF, et al., Bioconjug Chem. 2019 Jul 17;30(7):2049-2059
4. Synthesis of a Liposomal MUC1 Glycopeptide-Based Immunotherapeutic and Evaluation of the Effect of l- Rhamnose Targeting on Cellular Immune Responses. Karmakar P., et al., BioConjug Chem. 2016 Jan 20;27 (1):110-20
5. Synthesis of α-L-rhamnosyl ceramide and evaluation of its binding with anti-rhamnose antibodies. Long DE, et al., Bioorg Med Chem. 2014 Oct 1;22(19):5279-89.
6. Synthesis and immunological evaluation of a MUC1 glycopeptide incorporated into l-rhamnose displaying liposomes. Sarkar S., et al., Bioconjug Chem. 2013 Mar 20;24(3):363-
7. Synthesis of a single molecule L-rhamnose-containing three component vaccine and evaluation of antigenicity in the presence of anti L-rhamnose antibodies. Sarkar, S, et al., J. Am. Chem. Soc. 2010, 132, 17236–17246