BCG vaccination with adjunctive APRIL immunotherapy reduces tuberculosis relapse in mice

Area of Science:

• Immunology
• Infectious Diseases
• Vaccinology

Background:

• Bacille Calmette-Guérin (BCG) vaccination offers incomplete protection against tuberculosis (TB) relapse.
• Latent TB infection remains a significant challenge, necessitating improved therapeutic strategies.

Purpose of the Study:

• To evaluate the efficacy of B cell-targeted immunotherapy as an adjunct to BCG in a murine model of latent TB.
• To investigate the immunological mechanisms underlying enhanced BCG-mediated protection.

Main Methods:

• A murine model of latent tuberculosis was established.
• Mice received BCG vaccination followed by adjunctive immunotherapy with recombinant APRIL (a B cell-activating factor).
• Immune cell populations (B cells and T cells) and TB relapse rates were assessed.

Main Results:

• BCG vaccination alone provided only modest protection against TB relapse.
• Adjunctive immunotherapy with recombinant APRIL significantly reduced TB relapse rates compared to BCG alone.
• Protection was correlated with the activation and remodeling of marginal-zone B cell compartments, with minimal impact on T cell populations.

Conclusions:

• B cell-targeted immunotherapy, specifically with recombinant APRIL, can enhance BCG-mediated protection against tuberculosis relapse.
• The findings highlight the importance of B cell responses in controlling latent TB infection.
• Further research into B cell immunomodulation is warranted to develop more effective strategies for durable TB control.