Research Projects

Biotherapeutics, including monoclonal antibodies and therapeutic cytokines, are increasingly used for treating inflammatory diseases and cancers. However, the pharmaceutical industry faces challenges in maintaining these proteins in biologically active form for extended periods. Protein aggregation, which occurs during production, transport, and storage, can compromise the efficacy of these proteins by reducing the availability of active monomers and generating a neutralizing antibody response. The immunogenic response in monoclonal antibody aggregates is primarily due to their effective uptake, processing, and presentation by dendritic cells. The size and shape of protein aggregates can also influence the dendritic cell and B and T cell response. Protein aggregation can be controlled using standard biophysical methods for the discovery of novel biophysical entities. Protein antigens in supramolecular forms are expected to stay at the injection site for extended periods, avoiding the need for an adjuvant. When administered in a supramolecular form, an immunogen releases oligomers of varying size and shape, highlighting the potential of multimerizing motifs to induce self-assembly of protein molecules into large-size multimers. The proposed study will harness the potential of multimerizing motifs to induce multimerization of ovalbumin, a model antigen, and characterize the immune response to multimerized ovalbumin. This will demonstrate that multimerization of protein antigens can significantly enhance their uptake and presentation by antigen-presenting cells, thereby improving the immunogenicity and efficacy of current sub-unit vaccines and paving the way for the development of newer sub-unit vaccines.

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