Cytosol-Targeting Delivery of Non-Nucleotide STING Agonist Achieves Inhalable Nanoparticle-Based Anthrax Vaccine

Area of Science:

• Biotechnology
• Immunology
• Materials Science

Background:

• Inhalational anthrax poses a significant threat, with current vaccines having limitations in mucosal immunity and adjuvant delivery.
• There is a need for advanced vaccine platforms that can elicit robust and comprehensive immune responses.

Purpose of the Study:

• To develop and evaluate a novel self-assembling nanoparticle vaccine (YM1.7) for inhalational anthrax.
• To investigate the spatiotemporal delivery mechanism of antigens and adjuvants for enhanced immune responses.

Main Methods:

• YM1.7 nanoparticles were synthesized using polymers MP1, MP2, and STING agonist MSA-2, with recombinant protein antigen (rPA) conjugated to the surface.
• The vaccine was administered via aerosolized intratracheal inoculation in a mouse model.
• Immune responses, including innate, humoral, mucosal, and cell-mediated immunity, were assessed.

Main Results:

• YM1.7 nanoparticles were efficiently internalized by antigen-presenting cells and released their payload in a pH- and glutathione-dependent manner.
• The spatiotemporal release mechanism significantly enhanced the bioavailability of the STING agonist adjuvant in the cytosol.
• A coordinated innate, humoral, mucosal, and cell-mediated immune response was observed, providing strong protection against inhalational anthrax.

Conclusions:

• YM1.7 demonstrates a promising modular design for next-generation mucosal vaccines.
• This platform has potential applications beyond anthrax, including vaccines against other infections and cancers.