Engineered bacterial membrane vesicles as transdermal cancer vaccines

Area of Science:

• Biotechnology
• Immunology
• Materials Science

Background:

• Transdermal vaccines utilize skin's antigen-presenting cells (APCs) for immune responses.
• Effective transdermal delivery systems with adjuvant functions are crucial for vaccine success.

Purpose of the Study:

• To explore bacterial membrane vesicles (BMVs) as a nanoscale platform for transdermal vaccine engineering.
• To evaluate BMVs' transdermal penetration and immune-stimulating capabilities.

Main Methods:

• Engineered BMVs from VNP20009 with cholesterol-modified antigenic peptides for transdermal delivery.
• Compared skin penetration of BMVs and mammalian cell-derived membrane vesicles (CMVs).
• Assessed BMV-based vaccine effects on dendritic cell (DC) maturation, antigen cross-presentation, and T-cell immunity.

Main Results:

• BMVs demonstrated superior skin penetration via paracellular transport compared to CMVs.
• BMV-based vaccines stimulated DC maturation and enhanced antigen cross-presentation.
• Topical application of tumor-antigen-loaded BMVs induced robust anti-tumor immune responses and melanoma protection.

Conclusions:

• Bacterial membrane vesicles serve as a dual-function nanoscale platform for transdermal vaccines, acting as carriers and adjuvants.
• BMV-based transdermal vaccines effectively promote antigen-specific T-cell immunity and anti-tumor responses.