The Glycopeptide PV-PS A1 Immunogen Elicits Both CD4+ and CD8+ Responses
Sharmeen Nishat,
Md Kamal Hossain,
Geraud Valentin,
Farzana Hossain,
Shanika Gamage,
Katherine A. Wall,
Peter R. Andreana
Affiliations
Sharmeen Nishat
Department of Chemistry, Bangladesh University of Engineering and Technology (BUET), Dhaka 1000, Bangladesh
Md Kamal Hossain
Department of Medicinal and Biological Chemistry, College of Pharmacy and Pharmaceutical Sciences, The University of Toledo, 2801 West Bancroft Street, Toledo, OH 43606, USA
Geraud Valentin
Department of Chemistry and Biochemistry and School of Green Chemistry and Engineering, University of Toledo, 2801 West Bancroft Street, Toledo, OH 43606, USA
Farzana Hossain
Department of Chemistry and Biochemistry and School of Green Chemistry and Engineering, University of Toledo, 2801 West Bancroft Street, Toledo, OH 43606, USA
Shanika Gamage
Department of Chemistry and Biochemistry and School of Green Chemistry and Engineering, University of Toledo, 2801 West Bancroft Street, Toledo, OH 43606, USA
Katherine A. Wall
Department of Medicinal and Biological Chemistry, College of Pharmacy and Pharmaceutical Sciences, The University of Toledo, 2801 West Bancroft Street, Toledo, OH 43606, USA
Peter R. Andreana
Department of Chemistry and Biochemistry and School of Green Chemistry and Engineering, University of Toledo, 2801 West Bancroft Street, Toledo, OH 43606, USA
Background/Objectives: The MHCII-dependent, CD4+ T-cell zwitterionic polysaccharide PS A1 has been investigated as a promising carrier for vaccine development because it can induce an MHCII-dependent CD4+ response towards a variety of tumor-associated carbohydrate antigens (TACAs). However, PS A1 cannot elicit cytotoxic T lymphocytes through MHCI, which may or may not hamper its potential clinical use in cancer, infectious and viral vaccine development. This paper addresses PS A1 MHCI independence through the introduction of an MHCI epitope, the poliovirus (PV) peptide, to establish an MHCI- and MHCII-dependent vaccine. Methods: We synthesized a glycopeptide construct targeting the Thomsen-nouveau TACA (Tn-PV-PS A1) and a control Tn-PV peptide. C57BL/6 mice were immunized with both constructs, and the resulting T-cells were extracted from spleens. Results: Through cell proliferation assays, we show that Tn-PV-PS A1 elicits a robust CD4+ and CD8+ immune response. The resulting cytotoxic T lymphocytes are specific towards Tn-PV and trigger cell lysis of Tn-expressing EL4 cells. Conclusions: This study confirms PV-PS A1 as a robust MHCI- and MHCII-dependent carrier. This is the first report of MHCI dependence in a zwitterionic polysaccharide.
