Oxidative modifications of tuberculosis antigen Ag85B alter its T cell antigenicity.

Area of Science:

• Immunology
• Biochemistry
• Plasma Physics

Background:

• Tuberculosis (TB) remains a global health challenge, driving the need for advanced vaccine development.
• Oxidative stress at the host-pathogen interface is key, but its use to enhance antigen immunogenicity is underexplored.
• Reactive oxygen and nitrogen species (RONS) offer potential for antigen modification.

Purpose of the Study:

• To investigate the use of cold physical plasma to create oxidatively modified Ag85B (oxAg85B) variants.
• To assess the impact of these modifications on antigen immunogenicity and cellular immune responses.
• To explore the relationship between specific oxidative modifications and immune profiles.

Main Methods:

• Cold physical plasma was used to generate oxidatively modified Ag85B (oxAg85B).
• High-resolution mass spectrometry mapped 59 distinct oxidative protein post-translational modifications (oxPTMs).
• Transgenic mice with Ag85B-specific CD4+ T-cells were used to evaluate cellular immunity.

Main Results:

• Plasma treatment significantly enhanced Ag85B immunogenicity, boosting CD4+ T-cell activation and interferon-gamma secretion.
• The "redox fingerprint" of oxAg85B varied with plasma operational modes.
• Hydroxyl radical-rich plasma induced a Th17-biased profile, correlating IL-17α release with specific modifications (dihydroxylation, deamidation, carbonylation).

Conclusions:

• Oxidative modification of Ag85B via cold plasma selectively enhances cell-mediated immunity.
• Vaccination with oxAg85B increased systemic inflammatory cytokines without impacting anti-Ag85B antibody titers.
• This strategy offers a promising avenue for developing next-generation TB vaccines focusing on cellular immunity.