Porcine reproductive and respiratory syndrome (PRRS) is a major problem for hog farmers worldwide. PRRS is caused by a virus which leads to reproductive failure in...
Porcine reproductive and respiratory syndrome (PRRS) is a major problem for hog farmers worldwide. PRRS is caused by a virus which leads to reproductive failure in sows and respiratory problems in piglets and growing pigs. The PRRS virus spreads rapidly, leading to large economic losses for farmers and overall lower health for pigs. Currently, PRRS is controlled by inoculating pigs with modified live virus which stimulates the immune system of pigs against the PRRS virus. However, this therapy does not prevent PRRS virus infection and is limited by individual pigs ability to create a strong immune response against the vaccine. The current technology is a composition and method for use that enhances the immune response to PRRS vaccine for the purpose of improving the vaccines efficacy against the PRRS virus.
One of the challenges with PRRS is that the PRRS virus is resistant to pigs natural immune response. The PRRS virus is able to hide from the natural defense system by being resistant to signals that alert the body of the viruses presence. Interferon-a is one such alert signal that PRRS virus fails to up-regulate. The current technology uses plasmids (or related technologies) to increase interferon-a production during administration of modified live virus vaccine. By doing so, interferon-a interacts with T cells to create virus specific interferon-? secreting cells. The result is a robust immune system response to the vaccine which should strengthen the immune systems ability to fight infection of PRRS virus.
Applications
Can be used as a supplement to PRRS vaccines for swine
Has broad application for hog farmers and veterinary clinics
Benefits
Strengthened immune system: In vivo application of interferon-a and modified live virus to pigs resulted in over 3x as many virus specific interferon-? secreting cells as modified live virus application alone
Reduction in abortion/still births: Amount of PRRS virus specific interferon-? secreting cells is positively correlated with reduction of abortion/still births in sows
Exosomes are nano-sized vesicles secreted by cells that contain proteins, RNAs, polysaccharides, and lipids, playing a key role in cellular communication and holding...
Exosomes are nano-sized vesicles secreted by cells that contain proteins, RNAs, polysaccharides, and lipids, playing a key role in cellular communication and holding promise for diagnostic and therapeutic applications. Tumor-derived exosomes facilitate tumor progression and metastasis by transporting molecular messages and contribute to the immunosuppressive tumor microenvironment. They can penetrate blood vessels and circulate in the bloodstream, making them potential markers for cancer diagnosis. Exosomes also serve as a source of tumor antigens for cancer vaccines, which aim to generate antigen-specific immune responses. However, identifying tumor-specific antigens is complex and costly. Tumor exosome-based vaccines have shown promise in clinical trials but face challenges in effectively activating dendritic cells (DCs) and generating strong cytotoxic T lymphocyte (CTL) responses. The integration of adjuvants with tumor exosomes has not significantly improved vaccine potency due to differing trafficking and uptake profiles. There is a need for effective methods to conjugate adjuvants to exosomes to enhance their synergistic effects.
This technology is a method for development of personalized cancer vaccines using cancer cell-derived exosomes. Cancer cells collected from a patient can be labeled with unnatural sugars displaying the azide functional group. Exosomes generated from these cancer cells can be conjugated to adjuvants (or other tags or fluorescent dyes for diagnostic or research purposes) via click chemistry and reintroduced into the patient. Components of the exosome can be recognized as antigens and help the immune system in producing antigen-specific T cells and antibodies, showing a lower concentration of adjuvant is required to trigger the immune response.
Benefits
Conjugating adjuvant to exosomes improves immune response against cancer cells.
Lower concentration of potentially toxic adjuvant is required to trigger the immune response.
Publication Bhatta, R., Han, J., Liu, Y. et al. Metabolic tagging of extracellular vesicles and development of enhanced extracellular vesicle based cancer vaccines. Nat Commun 14, 8047 (2023). https://doi.org/10.1038/s41467-023-43914-8
