Spatiotemporal Dynamic Immunomodulation by Infection-Mimicking Gels Enhances Broad and Durable Protective Immunity...

Area of Science:

• Biomaterials Science
• Immunology
• Vaccinology

Background:

• Conventional subunit vaccines exhibit limitations including low immunogenicity, poor long-term immunity, and inadequate T-cell activation.
• Challenges persist in vaccine adaptation to rapidly evolving viral variants.

Purpose of the Study:

• To develop an infection-mimicking gel (IM-Gel) that enhances vaccine efficacy by emulating the spatiotemporal dynamics of immune stimulation during viral infections.
• To evaluate the IM-Gel's capacity for sustained delivery and enhanced retention of vaccine components in lymph nodes.

Main Methods:

• In situ supramolecular self-assembly of nanoparticulate toll-like receptor 7/8a (NP-TLR7/8a) and antigen with tannic acid (TA) to form the IM-Gel.
• Assessment of sustained delivery and retention of NP-TLR7/8a and antigen in mouse lymph nodes.
• Evaluation of humoral and cellular immune responses, including cross-protection against influenza subtypes and SARS-CoV-2 variants.

Main Results:

• The IM-Gel demonstrated sustained delivery and enhanced retention of vaccine components in lymph nodes for over 7 days.
• Robust humoral and cellular immune responses were observed, with prolonged exposure of vaccine components in B and T cell zones.
• IM-Gel formulations conferred cross-protection against multiple influenza subtypes and elicited strong cross-reactive antibody responses against SARS-CoV-2 variants.

Conclusions:

• The IM-Gel system effectively overcomes limitations of conventional vaccines by providing sustained immune stimulation.
• This programmable immunomodulatory material serves as a versatile platform for developing next-generation universal vaccines.
• The IM-Gel holds potential for eliciting broad and durable protective immunity against emerging viral pathogens.