Polyfunctional CD4⁺ T Cells As Targets for Tuberculosis Vaccination.

Area of Science:

• Immunology
• Vaccinology
• Infectious Diseases

Background:

• Tuberculosis (TB), caused by Mycobacterium tuberculosis (Mtb), is a major global health challenge.
• The current BCG vaccine offers limited protection, highlighting the need for more effective TB vaccines.
• Defining correlates of protection is essential for evaluating new TB vaccine candidates.

Purpose of the Study:

• To review literature on whether TB vaccines induce polyfunctional CD4+ T cells.
• To assess if these T cell responses correlate with vaccine-induced protection against TB.
• To identify potential correlates of protection for future TB vaccine development.

Main Methods:

• Systematic literature review of studies on BCG and novel TB vaccine candidates.
• Analysis of data on polyfunctional CD4+ T cell induction (IFN-γ, TNF-α, IL-2).
• Evaluation of reported correlations between T cell responses and protection in animal models and human studies.

Main Results:

• BCG and several novel TB vaccine candidates induce polyfunctional CD4+ T cells in animal models and humans.
• Studies in mouse models suggest an association between polyfunctional CD4+ T cells and protection.
• However, other studies in mice and human infants show no correlation, indicating polyfunctional T cells may not be a reliable correlate.

Conclusions:

• Polyfunctional CD4+ T cell induction is not sufficient, and possibly not necessary, for TB vaccine-mediated protection.
• Other T cell attributes (effector functions, differentiation, homing, survival) may be more critical for protection.
• A definitive correlate of protection for TB vaccine development is still elusive, requiring broader immunological assessments.