Table 2 Applications of outer membrane vesicles in medicine

Vaccine

Meningococcal vaccine generating FetA

The OMV-MenPF-1 vaccine was formed by genetically modified N. meningitidis strain 44/76 to generate FetA

Human vaccine for broad protection toward MenB infection

As PorA and FetA are used as part of the usual surveillance of meningococcal disorders, changes mediated to invasive meningococcal disease can be used to reform PorA/FetA vaccine combinations to maintain optimal coverage

[205]

N. gonorrhoea vaccine

Odds ratios comparing disorders outcomes in vaccinated individuals versus unvaccinated individuals by multivariable logistic regression

Cases include incidences of gonorrhoea, chlamydia, and co-infection. As well as controls

This vaccine has found protection against gonorrhoea that provides a proof of principle that can inform prospective vaccine development for N. gonorrhoea

[206]

Meningococcal Vaccine

(OMVs from N. lactamica)

The safety and immunogenicity of the vaccine N. lactamica OMV in the phase I clinical trial were evaluated

Ninety-seven healthy young adult male volunteers

Results showed this vaccine is safe and induces broad humoral immune reactions against N. meningitidis

[207]

Meningococcal vaccine

(A hexavalent PorA OMV)

Using five wild-type P1.19,15 variants (A hexavalent PorA OMV vaccine), the serum bactericidal antibody (SBA) titers in pre-and post-vaccination in phases I and II trialswere evaluated

Toddlers and schoolchildren

These findings found implications for the use of PorA as a meningococcal serogroup B vaccine

[208]

Meningococcal vaccine

Native OMV (NOMV) vaccine prepared from a lpxL2(−) synX(−) mutant of strain 44/76 with opcA expression stabilized

Thirty-four volunteers

These results suggest that genetically modified NOMV vaccines can induce protection against group B meningococcus

[209]

Adjuvant

OMV prepared from N. lactamica or N. meningitides

Mice were immunized with OMVs prepared from N. meningitidis and N. lactamica subcutaneously and intranasally

Mice

Results found that these OMVs are immunogenic when intranasally administered and act as effective intranasal adjuvants eliciting significantly increased IgA and IgG responses

[210]

Flagellin-deficient Salmonella Typhimurium OMVs

OMVs from flagellin-deficient S. Typhimurium and combined with outer membrane proteins from different Salmonella serotypes were purified and in vivo evaluated the response and cross-protection capacity to optimal vaccine composition

Mice

These OMVs induced significantly higher cellular immune reactions and displayed enhanced cross-protection for outer membrane proteins against wild-type virulent Salmonella

[211]

Penta acylated LPS-OMVs generated from ΔmsbB/ΔpagP mutant of E. coli W3110 (mOMV), and Hexa-acylated LPS-OMV generated from wild-type E. coliW3110 (wOMV)

T cell adjuvant activity of Penta acylated LPS-OMVs compared to Hexa-acylated LPS-OMVs. Penta-acylation of LPS renders mOMV less endotoxic than wOMV

Antigen-specific T cell priming in vitro and in vivo

It has been proposed that Penta acylated LPS-OMVs are a safe vaccine adjuvant for T cell priming and could further develop

[143]

Drug carrier

Transformed E. coli-derived OMVs, detoxified by lysozymes

Mice were subcutaneously and intranasally immunized with OMVs from N. meningitidis and N. lactamica, as well as live cells

The carrier for transdermal drug delivery

This study shows that transformed E. coli-derived OMVs, detoxified by lysozymes, are promising nanoplatforms in tumor targeting and drug delivery with high efficacy and biosafety

[212]

Delivering small interfering RNA (siRNA) targeting kinesin spindle protein (KSP)

Bioengineered bacterial OMVs with low immunogenicity that can target and kill cancer cells in a cell-specific manner by delivering siRNA targeting KSP were described

Cancer cells

These OMVs had the potential as cell-specific drug-delivery vehicles to treat some cancers

[199]

Cancer immunotherapy

Cancers

The potential of bacterial OMVs as therapeutic agents to treat cancer via immunotherapy was examined

Mice

Remarkable capability of bacterial OMVs to effectively induce long-term antitumor immune reactions that could eradicate established tumors without adverse effects. Moreover, these OMVs induce the production of antitumor cytokines interferon-gamma (IFN-γ) and C-X-C motif chemokine ligand 10 (CXCL10)

[189]

Cancers

(Differentially packaged sncRNAs in Helicobacter pylori OMVs)

Differentially packaged sncRNAs in H. pylori OMVs were identified, and OMV sncRNAs to human gastric adenocarcinoma cells were transferred

Human gastric adenocarcinoma cells (host mRNA)

It has been found that sR-2509025 and sR-989262 as sncRNAs that interact with host cells through OMV secretion and reduce the secretion of Interleukin 8 (IL-8), which targets mRNAs encoding multiple kinases in the LPS-stimulated mitogen-activated protein kinase (MAPK) signaling pathway, have not been thoroughly elucidated

[201]

Bacterial OMVs

A nanovaccine using bacterial biomembranes as carriers for antitumor therapy was developed. In this regard, the strong adjuvant effect of OMVs was used to induce the anti- basic fibroblast growth factor (BFGF) autoantibodies. The whole BFGF molecule was loaded onto OMVs and used for tumor therapy

Tumor

The current study found that OMVs successfully induce the persistent anti-BFGF autoantibodies to inhibit tumor growth and metastasis

[213]

Bactrial OMVs

OMVs- mesoporous silica (MSN)- 5-fluorouracil (5FU) were prepared by high-pressure co-extrusion, and size, drug loading, thermal gravity analysis, cytotoxicity, and cell uptake were characterized

Colon cancer

The study provided a promising nano platform for the targeting treatment of colon cancer

[214]

Biomarker

sRNA52320 in OMVs

RNA-Seq to characterize differentially packaged sRNAs in Pseudomonas aeruginosa OMVs was used, and transfer of OMV sRNAs to human airway cells was done

Human airway cells

These findings are consistent with the hypothesis that sRNA52320 in OMVs is a novel mechanism of host–pathogen interplays whereby some bacteria, such as P. aeruginosa, reduce the host immune reactions

[54]

Salivary OMV and DNA methylation of small extracellular vesicles

The healthy, gingivitis, and periodontitis groups were compared in terms of salivary extracellular vesicles in the CD9 + salivary extracellular vesicles subpopulation, Gram-negative bacteria-enriched LPS + OMVs, and global DNA methylation pattern of 5-methylcytosine (5mC), 5-hydroxymethylcytosine (5hmC), and N6-Methyladenosine (m6dA)

Healthy gingivitis and periodontitis individuals

The results show that global salivary extracellular vesicles methylation could be a potential biomarker for human periodontitis

[182]