Tuning Bacterial Morphology to Enhance Anticancer Vaccination

Area of Science:

• Biotechnology
• Immunology
• Microbial Engineering

Background:

• Morphology tuning is key for synthetic biomaterials but underexplored in microbe-based biochemicals.
• Microbial transformation offers a route to artificially adjust bacterial morphology.
• Escherichia coli was chosen as a model organism for morphology modification.

Purpose of the Study:

• To engineer filamentous morphology-adjusted bacteria (MABac) from Escherichia coli.
• To evaluate MABac as a bacteria-based vaccine adjuvant and carrier.
• To investigate the immunogenicity and in vivo activity of MABac compared to parent bacteria.

Main Methods:

• Chemical stimulation was used to induce filamentous morphology in Escherichia coli.
• Inactivated MABac were prepared for use as a vaccine adjuvant/carrier.
• Transcriptomic analysis was performed to understand in vivo immune responses.
• In vivo studies assessed the delivery patterns and immunogenicity of MABac.

Main Results:

• MABac exhibited enhanced immunogenicity and distinct delivery patterns (phagosome escape, cytoplasmic retention) compared to parent bacteria (Bac).
• Transcriptomic data revealed MABac activates cytosolic immune pathways (NOD-like receptors, STING), inducing broader immune responses.
• MABac-based adjuvant/carrier significantly improved cancer antigen delivery and immunogenicity in vivo.
• Enhanced cancer-specific immunity was observed against a melanoma challenge.

Conclusions:

• Bacterial morphology tuning is a feasible strategy to enhance biological effects.
• This study establishes a facile engineering approach to upgrade bacterial properties without gene editing.
• MABac represents a promising bacteria-based adjuvant/carrier for improved vaccine efficacy, particularly in cancer immunotherapy.