MAIT cell activation augments adenovirus vector vaccine immunogenicity

Area of Science:

• Immunology
• Vaccinology
• Infectious Diseases

Background:

• Mucosal-associated invariant T (MAIT) cells are innate immune sensors with roles in antiviral responses.
• Adenovirus vectors are widely used in vaccine platforms, but their immunogenicity can be further optimized.

Purpose of the Study:

• To investigate the role and activation mechanisms of MAIT cells in response to adenovirus vector-based vaccines.
• To determine if MAIT cells possess inherent adjuvant activity in chimpanzee adenovirus Oxford 1 (ChAdOx1) vaccine platforms.

Main Methods:

• Immunization of mice and analysis of human volunteers receiving ChAdOx1 vaccine.
• In vitro and in vivo experiments to identify key cytokines (IFN-α, IL-18, TNF) involved in MAIT cell activation.
• Assessment of T cell responses in MAIT cell-deficient mice and human volunteers.

Main Results:

• ChAdOx1 immunization robustly activated MAIT cells in both mice and humans.
• MAIT cell activation was dependent on plasmacytoid dendritic cell-derived interferon-alpha (IFN-α) and monocyte-derived interleukin-18 (IL-18), with tumor necrosis factor (TNF) as a secondary signal.
• MAIT cell activation correlated with enhanced T cell responses, and MAIT cell-deficient mice showed impaired CD8+ T cell immunity.

Conclusions:

• MAIT cells are crucial contributors to the immunogenicity of adenovirus vector vaccines.
• The findings highlight the potential of MAIT cells as a target for enhancing vaccine efficacy.
• Understanding MAIT cell activation pathways offers new avenues for next-generation vaccine design.