Photo: Bryan Goodchild
Research by Katherine A. Fitzgerald, PhD, the Worcester Foundation for Biomedical Research Chair III, professor and executive vice chair of medicine, vice provost for basic science research and chief of the division of innate immunity, in collaboration with Elicio Therapeutics, Inc., shows potential for increasing vaccine efficacy. The findings, published in Science Advances, have the potential to transform otherwise weak vaccine adjuvants into powerful innate immune system stimulators, opening new avenues for treatment of infections and cancer. Through their research, UMass Chan scientists have discovered how a novel vaccine platform using amphiphile (AMP) modified DNA adjuvants that target the lymph nodes stimulate the innate immune system to generate a potent T-cell response.
“AMP modified DNA adjuvants represent an exciting step forward in innate immune stimulation and vaccine platform development,” said Dr. Fitzgerald. “These adjuvants generate a potent immune response by engaging inflammatory pathways that are crucial for vaccine efficacy. By making the immune system recognize the vaccine better, the platform can potentially increase effectiveness, allow for smaller dosage sizes and a lower number of shots required.”
Adjuvants, pharmacological additives formulated to boost and shape the body’s immune response or deliver antigens, are present in almost all vaccines. They make vaccines more effective and longer lasting by enhancing the immune system’s ability to recognize pathogenic antigens. However, these adjuncts, the most common of which are aluminum salts, often are unable to elicit the long-term immunity or strong cellular immune response necessary for protection against pathogens such as malaria, tuberculosis and other viruses, because they diffuse away before reaching the immune system’s command centers.
Experiments by Wei Zhan, a PhD student in the Fitzgerald lab, showed that the AMP modified adjuvants were jumpstarting the innate immune system by stimulating the TANK-binding kinase TBK1. This danger-sensing pathway generated strong innate immune responses which in turn promote robust adaptive immunity and long-term immune response memory with potent recall potential by driving robust production of interferon type-I, the body’s early-warning system against pathogens. Interferon production then stimulates antiviral defenses in nearby healthy cells – in this case production of CD8 and CD4 T-cells.
“This study highlights our ability to precisely direct immune activation to the lymph nodes and unlock powerful, durable T cell responses through novel mechanisms, such as TBK1 and type I interferon (IFN-I) signaling. We believe these new AMP-DNA immuno-activators represent a meaningful step toward expanding the AMP toolkit of next-generation immunotherapies across oncology and infectious disease,” said Peter DeMuth, PhD, chief scientific officer of Elicio.
Elicio provided the AMP modified reagents to the Fitzgerald lab. The funding for the pilot study came from the Worcester Foundation for Biomedical Research Chair III. Data generated from this work will be used to apply for grant funding to further investigate the underlying mechanisms driving the innate immune response to these adjuvants.
