Antigen-specific antibody and polyfunctional T cells generated by respiratory immunization with protective...

Area of Science:

• Immunology
• Vaccinology
• Microbiology

Background:

• Melioidosis, a severe infectious disease, is caused by the bacterium Burkholderia pseudomallei (Bpm).
• Currently, no effective vaccine is available for melioidosis prevention.
• Understanding the immune responses that confer protection is essential for vaccine development.

Purpose of the Study:

• To identify immune correlates of protection against inhalational melioidosis.
• To evaluate the efficacy of two experimental vaccines, B. mallei ΔtonB Δhcp1 (CLH001) and Bpm ΔtonB Δhcp1 (PBK001).

Main Methods:

• Mucosal immunization with CLH001 and PBK001 vaccines in a preclinical model.
• Analysis of Bpm-specific antibody isotypes (IgM, IgG, IgA) in serum and lung.
• Assessment of cellular immune responses, including CD4+ T-cell recall and polyfunctional memory pools.
• Evaluation of serum bactericidal activity and opsonophagocytic uptake.
• Histological analysis of lung tissue post-challenge.

Main Results:

• Both vaccines induced Bpm-specific IgM, IgG, and lung IgA antibodies.
• Vaccine-induced serum showed complement-independent bactericidal activity and promoted macrophage opsonophagocytosis.
• Both vaccines elicited Th1 and Th17 CD4+ T-cell responses.
• The PBK001 vaccine demonstrated superior induction of respiratory IgA, anamnestic IgG, and diverse polyfunctional memory T-cells.
• PBK001-induced T-cell memory and IL-17 signatures correlated with moderate lung inflammation.

Conclusions:

• Mucosal immunization with CLH001 and PBK001 vaccines elicits significant humoral and cellular immune responses against Bpm.
• The PBK001 vaccine is more effective in generating protective immune responses, including robust T-cell memory.
• Polyfunctional T-cell memory and IL-17 may play a role in protection and modulating lung inflammation in melioidosis.