Targeted Exosomes mediated cellular delivery: A potential approach for vaccine development
Implementing Organization
Principal Investigator
Prof. Madhu Khanna
Vallabhbhai Patel Chest Institute, New Delhi
Project Overview
One of the major concerns to achieve desirable immunity after influenza virus vaccination is the generation of strong T cell immune responses. Given the COVID-19 pandemic and continued circulation of SARS-CoV-2 viruses, it is imperative to mitigate the enhanced risk of respiratory infections imposed by influenza viruses. In the present research project, we propose a novel approach to enable robust and broad-spectrum T-cell mediated immune responses by targeted delivery of engineered exosomes to the antigen presenting dendritic cells. We aim to engineer exosomes to express anti-CRD-2(DEC-205) receptor over the exosome surface to enable specific delivery of highly conserved influenza virus NP or PB1 T-cell epitope(s) to the dendritic cells. By this, we intend to generate robust and broad-spectrum T-cell mediated immune responses. The proposed work will be evaluated under both in vitro (DC cell line) and in vivo (BALB/c mice) conditions. Since exosomes are natural biological nanovesicles, we expect to generate robust T cell immune responses against influenza viruses in cell line as well as in animal model without cellular toxicity or any other after-effect. Furthermore, we aim to engineer the exosomes to express the anti-DEC-205 antibody that will specifically bind and thus, deliver the antigenic cargo to the DC only to enable enhanced T-cell immune responses. The DEC-205 is an endocytic receptor that is extensively expressed in several human and murine leukocyte populations. Hence, DEC-205 offers variety of clinical applications. The proposed strategy may overcome the limitations of vaccine and may also serve as a treatment alternative. A similar approach may also have applications in cancer and other infectious diseases of major concern in India and other developing countries.