Bacterial protoplast-derived nanovesicles as vaccine delivery system against bacterial infection.

The notion that widespread infectious diseases could be best managed by developing potent, adjuvant-free vaccines has resulted in the use of various biological immune-stimulating components as new vaccine candidates. Recently, extracellular vesicles, also known as exosomes and microvesicles in mammalian cells and outer membrane vesicles in Gram-negative bacteria, have gained attention for the next generation vaccine. However, the more invasive and effective the vaccine is in delivery, the more risk it holds for severe immune toxicity. Here, in optimizing the current vaccine delivery system, we designed bacterial protoplast-derived nanovesicles (PDNVs), depleted of toxic outer membrane components to generate a universal adjuvant-free vaccine delivery system. These PDNVs exhibited significantly higher productivity and safety than the currently used vaccine delivery vehicles and induced strong antigen-specific humoral and cellular immune responses. Moreover, immunization with PDNVs loaded with bacterial antigens conferred effective protection against bacterial sepsis in mice. These nonliving nanovesicles derived from bacterial protoplast open up a new avenue for the creation of next generation, adjuvant-free, less toxic vaccines to be used to prevent infectious diseases.

[1]  Wei Zhang,et al.  A peptide-based nanofibrous hydrogel as a promising DNA nanovector for optimizing the efficacy of HIV vaccine. , 2014, Nano letters.

[2]  Vipul Gujrati,et al.  Bioengineered bacterial outer membrane vesicles as cell-specific drug-delivery vehicles for cancer therapy. , 2014, ACS nano.

[3]  S. Chisholm,et al.  Bacterial Vesicles in Marine Ecosystems , 2014, Science.

[4]  Jaesung Park,et al.  Bioinspired exosome-mimetic nanovesicles for targeted delivery of chemotherapeutics to malignant tumors. , 2013, ACS nano.

[5]  Jaesung Park,et al.  Three-Dimensional Imaging of Hepatic Sinusoids in Mice Using Synchrotron Radiation Micro-Computed Tomography , 2013, PloS one.

[6]  Tae-Young Roh,et al.  Immunization with Escherichia coli Outer Membrane Vesicles Protects Bacteria-Induced Lethality via Th1 and Th17 Cell Responses , 2013, The Journal of Immunology.

[7]  C. Harding,et al.  Exosomes: Looking back three decades and into the future , 2013, The Journal of cell biology.

[8]  J. Hubbell,et al.  Nanoparticle size influences the magnitude and quality of mucosal immune responses after intranasal immunization. , 2012, Vaccine.

[9]  A. Marcilla,et al.  Extracellular Vesicles from Parasitic Helminths Contain Specific Excretory/Secretory Proteins and Are Internalized in Intestinal Host Cells , 2012, PloS one.

[10]  L. D. Britt,et al.  Circulating Bacterial Membrane Vesicles Cause Sepsis in Rats , 2012, Shock.

[11]  H. D. del Portillo,et al.  Exosomes from Plasmodium yoelii-Infected Reticulocytes Protect Mice from Lethal Infections , 2011, PloS one.

[12]  Brenda S. Collins,et al.  Gram-negative outer membrane vesicles in vaccine development. , 2011, Discovery medicine.

[13]  Wah Chiu,et al.  Interbilayer-Crosslinked Multilamellar Vesicles as Synthetic Vaccines for Potent Humoral and Cellular Immune Responses , 2011, Nature materials.

[14]  C. Poh,et al.  Protective Efficacy of DNA Vaccines Encoding Outer Membrane Protein A and OmpK36 of Klebsiella pneumoniae in Mice , 2010, Clinical and Vaccine Immunology.

[15]  Martin F. Bachmann,et al.  Vaccine delivery: a matter of size, geometry, kinetics and molecular patterns , 2010, Nature Reviews Immunology.

[16]  M. Kuehn,et al.  Biological functions and biogenesis of secreted bacterial outer membrane vesicles. , 2010, Annual review of microbiology.

[17]  D. Missiakas,et al.  Contribution of Coagulases towards Staphylococcus aureus Disease and Protective Immunity , 2010, PLoS pathogens.

[18]  A. Kimura,et al.  IL‐6: Regulator of Treg/Th17 balance , 2010, European journal of immunology.

[19]  J. Kim,et al.  Outer Membrane Vesicles Derived from Escherichia coli Induce Systemic Inflammatory Response Syndrome , 2010, PloS one.

[20]  Rino Rappuoli,et al.  Identification of protective and broadly conserved vaccine antigens from the genome of extraintestinal pathogenic Escherichia coli , 2010, Proceedings of the National Academy of Sciences.

[21]  S. Akira,et al.  Pattern Recognition Receptors and Inflammation , 2010, Cell.

[22]  Yung-Fu Chang,et al.  Identification and characterization of OmpA-like proteins as novel vaccine candidates for Leptospirosis. , 2010, Vaccine.

[23]  D. Granoff.  Review of meningococcal group B vaccines. , 2010, Clinical infectious diseases : an official publication of the Infectious Diseases Society of America.

[24]  T. Ficht,et al.  Polymeric particles in vaccine delivery. , 2010, Current opinion in microbiology.

[25]  D. Putnam,et al.  Delivery of foreign antigens by engineered outer membrane vesicle vaccines , 2010, Proceedings of the National Academy of Sciences.

[26]  Y. Gho,et al.  Gram‐positive bacteria produce membrane vesicles: Proteomics‐based characterization of Staphylococcus aureus‐derived membrane vesicles , 2009, Proteomics.

[27]  C. Théry,et al.  Membrane vesicles as conveyors of immune responses , 2009, Nature Reviews Immunology.

[28]  Y. Gho,et al.  Proteomics in gram-negative bacterial outer membrane vesicles. , 2008, Mass spectrometry reviews.

[29]  W. Paul,et al.  CD4 T cells: fates, functions, and faults. , 2008, Blood.

[30]  Stephen G. J. Smith,et al.  A molecular Swiss army knife: OmpA structure, function and expression. , 2007, FEMS microbiology letters.

[31]  Thomas C. Mitchell,et al.  The Vaccine Adjuvant Monophosphoryl Lipid A as a TRIF-Biased Agonist of TLR4 , 2007, Science.

[32]  J. Lötvall,et al.  Exosome-mediated transfer of mRNAs and microRNAs is a novel mechanism of genetic exchange between cells , 2007, Nature Cell Biology.

[33]  I. Aaberge,et al.  Immunogenicity and safety of a strain-specific MenB OMV vaccine delivered to under 5-year olds in New Zealand. , 2007, Vaccine.

[34]  G. Grandi,et al.  Outer membrane vesicles from group B Neisseria meningitidis Δgna33 mutant: Proteomic and immunological comparison with detergent‐derived outer membrane vesicles , 2006, Proteomics.

[35]  K. Tracey,et al.  Vagus nerve stimulation attenuates the systemic inflammatory response to endotoxin , 2000, Nature.

[36]  J. Venter,et al.  Identification of vaccine candidates against serogroup B meningococcus by whole-genome sequencing. , 2000, Science.

[37]  G. Archer.  Staphylococcus aureus: a well-armed pathogen. , 1998, Clinical infectious diseases : an official publication of the Infectious Diseases Society of America.

[38]  Laurence Zitvogel,et al.  Eradication of established murine tumors using a novel cell-free vaccine: dendritic cell derived exosomes , 1998, Nature Medicine.

[39]  Shinobu Ueda,et al.  Systemically Injected Exosomes Targeted to EGFR Deliver Antitumor MicroRNA to Breast Cancer Cells. , 2013, Molecular therapy : the journal of the American Society of Gene Therapy.

[40]  J. Keenan,et al.  A role for the bacterial outer membrane in the pathogenesis of Helicobacter pylori infection. , 2000, FEMS microbiology letters.