STING Agonists as Immunomodulators and Vaccine Adjuvants
STING agonists proven to be effective vaccine adjuvants and immunomodulators in newborns
Background
Infectious diseases are the leading cause of morbidity and mortality in early life and immunization is a key preventive strategy. Vaccine adjuvants can enhance, prolong, and modulate immune responses to vaccinal antigens to maximize protective immunity, and may potentially enable effective immunization in challenging populations (e.g., in the very young and the elderly or for diseases lacking effective vaccines). Immunization of newborns and infants, however, results in sub optimal responses, and often requires multiple booster doses and can be limited by waning immunity.
Technology Overview
Stimulator of Interferon Genes (STING) agonists are effective adjuvants active in both early life and in adulthood. Researchers at Boston Children's Hospital have discovered that the unexpected combination of STING and\ TLR7/8 agonists synergistically activate immune Th1Hpolarizing responses of human newborn and adult DCs that may be important for vaccine induced protection against intracellular pathogens. Preliminary data indicate that STING can enhance vaccine responses in newborn mice, and further in vivo data are being developed to further characterize the potential of combinations of STING and TLR7/8 agonists as a novel early life vaccine adjuvant system.
Further Details:
- Borriello F, Pietrasanta C, Lai JCY, et al. Identification and Characterization of Stimulator of Interferon Genes As a Robust Adjuvant Target for Early Life Immunization. Front Immunol. 2017;8:1772. Published 2017 Dec 12. doi:10.3389/fimmu.2017.01772
Stage of Development
Proof of concept:
• TLR7/8 agonists, such as the small imidazoquinoline molecules induced the highest cytokine production (TNF, ILH6) by neonatal and adult murine DCs
• STING agonist, such as the molecule cGAMP, induced the highest levels of expression of surface costimulatory molecules, such as CD40, CD80, CD86.
• Combination of STING and TLR7/8 agonists synergistically upregulated the production of TNF, type I interferon (IFNβ), and the expression of surface costimulatory molecules in both murine newborn and adult DCs.
• in vivo studies in a newborn murine model of influenza immunization indicated that STING agonist enhance vaccine responses of neonatal mice compared to aluminum (Alum), a standard early life vaccine adjuvant.
• Immunization with recombinant hemagglutinin (rHA) formulated with cGAMP and alum induced distinct antibody profiles in adult and newborn mice (Figure).
Benefits
STING agonists proven to be effective vaccine adjuvants and immunomodulators in newborns
Applications
- Vaccine adjuvants
- Immunomodulation
IP Status
