Outer membrane vesicles engineered to express membrane-bound antigen program dendritic cells for cross-presentation...

Area of Science:

• Immunology
• Vaccinology
• Bacteriology

Background:

• Outer membrane vesicles (OMVs) from Gram-negative bacteria are emerging as vaccine vectors.
• OMVs are naturally adjuvant-rich and can be engineered to display specific antigens.
• Their ability to induce T cell responses, particularly CD8+ T cells, requires further investigation.

Purpose of the Study:

• To investigate whether OMVs induce dendritic cell (DC)-mediated antigen-specific T cell responses.
• To elucidate the mechanisms underlying OMV-induced immune activation and antigen presentation.
• To establish OMVs as effective carriers for CD8+ T cell-inducing vaccines.

Main Methods:

• OMVs were produced from a hypervesiculating Salmonella typhimurium strain.
• OMVs were used to stimulate human and murine dendritic cells (DCs).
• DC maturation, survival, and antigen cross-presentation to T cells were assessed.
• Molecular pathways involving LPS, MyD88, and BATF3 were analyzed.

Main Results:

• OMVs induced DC maturation, dependent on lipopolysaccharide (LPS) and MyD88 signaling.
• OMVs enhanced DC survival without inducing cell death.
• Engineered OMVs displaying antigens induced potent, MyD88-dependent cross-presentation to CD8+ T cells.
• Cross-presentation was partly independent of the BATF3-dependent DC subset.

Conclusions:

• OMVs program DCs for maturation and survival, facilitating antigen presentation.
• OMVs are effective vehicles for inducing antigen-specific CD8+ T cell responses.
• This study provides mechanistic insights into OMV-DC interactions for therapeutic vaccine development.