The study of fully synthetic carbohydrate vaccines has been ongoing for over a decade. A typical fully synthetic carbohydrate vaccine includes a carbohydrate antigen, T-helper cell epitope and immunoadjuvant to boost the immune response. Many modifications of this primary design are being explored in order to achieve an optimal immune response against the antigens. Anti-rhamnose antibodies are one of the most common natural antibodies found in human serum. In our earlier studies, we have shown that use L-rhamnose as an antibody recruiting molecule is an effective way to enhance processing and presentation of antigen by antigen presenting cells (APCs) using anti-rhamnose antibodies generated in mice. In the present study, we evaluate human anti-rhamnose antibodies isolated using affinity purification from human serum. We synthesized an anticancer vaccine construct consisting MUC-1 Tn glycopeptide, a Tumor Associated Carbohydrate Antigen (TACA) along with CD8+ T- cell epitope and Pam3CysSK4 , a Toll-like receptor-2 ligand as an immuno-adjuvant. Strain promoted alkyne-azide cycloaddition (SPAAC) was used to conjugate Pam3CysSK4 to the MUC-1 antigen. The construct along with Rhamnose-Cholesterol were incorporated into liposomes by the extrusion method. Isolated human anti-rhamnose antibodies were administered to C57BL6 mice prior to immunization with the liposomal MUC-1 Tn vaccine. Immunological evaluation showed increased priming of both CD4+ and CD8+ T cells toward the MUC1-Tn cancer antigen. Therefore, we have confirmed that adoptive transfer of human anti-rhamnose antibodies to mice can enhance immune response against a rhamnose containing vaccine. Also the use of affinity purified anti-rhamnose antibodies improved the efficacy of vaccine.

Synthesis of multi-component anti-tumor vaccine using strain promoted azide alkyne cycloaddition (SPAAC) and enhancement of immune response using human anti-rhamnose antibodies

254th National Meeting (2017)

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