Lymph Node Follicle-Targeting STING Agonist Nanoshells Enable Single-Shot M2e Vaccination for Broad and Durable...

Area of Science:

• Vaccinology
• Nanotechnology
• Immunology

Background:

• The matrix protein 2 ectodomain (M2e) is a conserved influenza antigen, but its low immunogenicity hinders vaccine development.
• Developing effective vaccines against mutation-prone influenza viruses remains a global health challenge.

Purpose of the Study:

• To create a potent nanovaccine using M2e peptides and STING agonists for broad and durable influenza protection.
• To investigate the mechanisms underlying the enhanced immunogenicity induced by the M2e nanoshell vaccine.

Main Methods:

• Polymeric nanoshells were synthesized via asymmetric ionic stabilization, co-encapsulating high densities of M2e peptides and STING agonists.
• The M2e nanoshell vaccine's efficacy and durability were evaluated in mice against heterotypic influenza viruses.
• Immunological responses, including humoral immunity and T cell functions, were analyzed.

Main Results:

• A single administration of M2e nanoshells conferred robust and long-lasting protection against heterotypic influenza viruses in mice.
• The STING agonist acted as a molecular adjuvant, prolonging M2e antigen exposure in lymph node follicles.
• Enhanced anti-M2e humoral responses were observed, characterized by Th1-biased antibody production.

Conclusions:

• The M2e nanoshell vaccine design effectively enhances the immunogenicity of weak antigens by leveraging innate immune pathways.
• This single-shot nanovaccine platform offers a translationally viable approach for pandemic preparedness against influenza.