# Tiny packages, big potential: bacterial membrane vesicles in vaccinology

**Authors:** Ayşe Varol, Şeyma Aydın, Ahmet Adıgüzel, Selçuk Özdemir

PMC · DOI: 10.1186/s12934-025-02908-5 · 2025-12-30

## TL;DR

Bacterial membrane vesicles (BMVs) are being explored as safe and effective vaccine platforms due to their ability to modulate the immune system and deliver antigens.

## Contribution

The paper reviews recent advances in BMV engineering and bioprocessing for next-generation vaccine development.

## Key findings

- BMVs resemble eukaryotic extracellular vesicles and can be engineered for antigen display.
- Licensed OMV vaccines demonstrate their safety and immunogenicity.
- Innovations in bioprocessing improve BMV scalability and mucosal delivery.

## Abstract

Bacterial membrane vesicles (BMVs) are nanoscale, bilayered proteolipid structures secreted by both Gram-negative and Gram-positive bacteria. Initially considered cellular debris, BMVs are now recognized as evolutionarily conserved entities with critical roles in bacterial communication, immune modulation, virulence factor delivery, and horizontal gene transfer. Their structural and functional resemblance to eukaryotic extracellular vesicles has fueled growing interest in their use as versatile vaccine platforms. Licensed meningococcal OMV vaccines established proof-of-concept for their safety and immunogenicity, and ongoing studies are extending applications to enteric pathogens and viral infections. Recent advances in genetic engineering, glycoengineering, and modular antigen display systems have enabled the design of “plug-and-play” BMVs with reduced reactogenicity and enhanced protective efficacy. In parallel, innovations in bioprocessing and formulation technologies are improving scalability, stability, and delivery, including mucosal routes. This review highlights the immunological properties, translational potential, and key challenges of BMV-based vaccines, with an emphasis on strategies to optimize safety, antigen specificity, and manufacturing for next-generation vaccine development.

## Full-text entities

- **Diseases:** Shigellosis (MESH:D004405), toxicity (MESH:D064420), OMVs (MESH:D015433), infectious (MESH:D003141), cancer (MESH:D009369), Neisseria meningitidis (MESH:D006069), enteric pathogens (MESH:D004751), COVID-19 (MESH:D000086382), viral infections (MESH:D014777), meningococcal disease (MESH:D008589), influenza (MESH:D007251), nasal irritation (MESH:D009668), inflammation (MESH:D007249)
- **Chemicals:** chitosan (MESH:D048271), PE (MESH:C483858), O-antigen (MESH:D019081), lipooligosaccharides (MESH:C023023), Aluminum hydroxide (MESH:D000536), Lipids (MESH:D008055), oligosaccharide (MESH:D009844), CpG (MESH:C015772), PG (MESH:D010715), -antigen polysaccharides (-), MF59 (MESH:C089950), carbohydrate (MESH:D002241), acids (MESH:D000143), stearic acid (MESH:C031183), MPLA (MESH:C048436), ATP (MESH:D000255), cardiolipin (MESH:D002308), GMMAs (MESH:C043583), polysaccharide (MESH:D011134), luminal (MESH:D010634), CpG oligodeoxynucleotides (MESH:C408982), LPS (MESH:D008070), Phospholipids (MESH:D010743), lyso-PE (MESH:C008301), poly(anhydride) (MESH:D049388), aluminum (MESH:D000535), glycerophospholipids (MESH:D020404), cholesterol (MESH:D002784), Lipid A (MESH:D008050), polyacrylamide (MESH:C016679)
- **Species:** Helicobacter pylori (species) [taxon 210], Burkholderia pseudomallei (species) [taxon 28450], Pseudomonas syringae (species) [taxon 317], Neisseria meningitidis (species) [taxon 487], Bacteria Latreille et al. 1825 (Bacteria stick insect, genus) [taxon 629395], Enterobacter cloacae (species) [taxon 550], Haemophilus influenzae (species) [taxon 727], Neisseria gonorrhoeae (species) [taxon 485], Vibrio cholerae (species) [taxon 666], Middle East respiratory syndrome-related coronavirus (no rank) [taxon 1335626], Aggregatibacter actinomycetemcomitans (species) [taxon 714], Acinetobacter baumannii (species) [taxon 470], Streptococcus suis (species) [taxon 1307], Shigella flexneri 2a (serotype) [taxon 42897], Salmonella enterica (species) [taxon 28901], Shigella flexneri (species) [taxon 623], Treponema denticola (species) [taxon 158], Mus musculus (house mouse, species) [taxon 10090], Severe acute respiratory syndrome coronavirus 2 (no rank) [taxon 2697049], Escherichia coli (E. coli, species) [taxon 562], Cricetinae (hamsters, subfamily) [taxon 10026], Salmonella enterica subsp. enterica serovar Typhimurium (no rank) [taxon 90371], Porphyromonas gingivalis (species) [taxon 837], Oryctolagus cuniculus (domestic rabbit, species) [taxon 9986], Escherichia coli str. K-12 substr. MG1655 (no rank) [taxon 511145], Shigella sonnei (species) [taxon 624], Bordetella pertussis (species) [taxon 520], Pseudomonas aeruginosa (species) [taxon 287], Homo sapiens (human, species) [taxon 9606]

## Figures

2 figures with captions in the complete paper: https://tomesphere.com/paper/PMC12859873/full.md

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Source: https://tomesphere.com/paper/PMC12859873