Nanoscale Peptide Self-assemblies Boost BCG-primed Cellular Immunity Against Mycobacterium tuberculosis

Area of Science:

• Immunology
• Vaccinology
• Infectious Diseases

Background:

• Bacillus Calmette-Guerin (BCG) is the sole tuberculosis (TB) vaccine, but its protective efficacy is limited and wanes over time.
• Multifunctional CD8+ T cells (producing IFN-γ, TNF-α, and IL-2) are crucial for controlling Mycobacterium tuberculosis (Mtb) infection.
• Boosting BCG vaccination is contraindicated, necessitating novel strategies to enhance T cell immunity in BCG-vaccinated individuals.

Purpose of the Study:

• To develop and evaluate a novel booster vaccine strategy using peptide nanofibers to augment T cell immunity in BCG-vaccinated individuals.
• To assess the ability of intranasally administered peptide nanofibers presenting Mtb-specific epitopes to induce antigen-specific T cell responses in the lungs.
• To determine if co-administration of TLR2 agonists with peptide nanofibers enhances CD8+ T cell responses and confers improved protection against Mtb challenge.

Main Methods:

• Development of self-assembling peptide nanofibers presenting Mtb-specific CD8+ or CD4+ T cell epitopes.
• Intranasal immunization of mice with peptide nanofibers, with or without TLR2 agonists.
• Assessment of antigen-specific CD8+ T cell populations and cytokine production (IFN-γ, IL-2) in the lungs via flow cytometry.
• Evaluation of vaccine efficacy through aerosol challenge with Mtb and measurement of bacterial load in the lungs.

Main Results:

• Intranasal immunization with peptide nanofibers induced antigen-specific CD8+ T cell populations in the lungs.
• Co-administration of Mtb CD8+ T cell epitope nanofibers with TLR2 agonists resulted in an 8-fold expansion of multifunctional CD8+ T cells in the lungs.
• BCG-primed and nanofiber-boosted mice showed a 0.5-log CFU reduction in lung bacterial load compared to BCG vaccination alone after Mtb challenge.

Conclusions:

• Heterologous prime-boost vaccination with BCG and peptide nanofibers effectively induces cell-mediated immunity in the lungs.
• This strategy enhances protection against Mtb infection by reducing bacterial burden.
• Peptide nanofiber vaccines represent a promising and potentially safer alternative for boosting BCG-primed immunity against tuberculosis.