Persistent BCG bacilli perpetuate CD4 T effector memory and optimal protection against tuberculosis.

Area of Science:

• Immunology
• Vaccinology
• Microbiology

Background:

• Tuberculosis (TB) remains a major global health challenge, necessitating improved vaccines beyond the current Bacillus Calmette-Guérin (BCG) vaccine.
• Understanding the immunological mechanisms of BCG-induced protection is crucial for developing next-generation TB vaccines.

Purpose of the Study:

• To investigate the long-term persistence of BCG vaccine bacilli in a murine model.
• To determine the influence of persistent BCG on immune responses and protection against TB.
• To differentiate between long-lived memory cells and responses driven by persistent bacilli.

Main Methods:

• Long-term BCG vaccination in a murine model.
• Monitoring BCG bacilli persistence.
• Assessing CD4 T-cell effector/TEM and tetramer-specific responses.
• Evaluating TB protection after clearing persistent BCG bacilli.

Main Results:

• Viable BCG bacilli persisted for at least 16 months post-vaccination.
• Persistent BCG was associated with sustained CD4 T-cell effector/TEM and tetramer-specific responses.
• Clearing persistent BCG abrogated BCG-specific CD4 T cells but only reduced protection by 1 log10.

Conclusions:

• BCG may induce additive immunity through mechanisms dependent and independent of persistent bacilli.
• Persistent BCG bacilli contribute to specific T-cell responses, but protection is not solely reliant on them.
• These findings have significant implications for designing novel TB vaccines and interpreting BCG immunity studies.