Stability of mono- and trivalent meningococcal outer membrane vesicle vaccines

Arigita, Carmen; Jiskoot, Wim; Westdijk, Janny; Ingen, Cor van; Hennink, Wim E.; Crommelin, Daan J.A.; Kersten, Gideon

doi:10.1016/j.vaccine.2003.08.027

Cited by 59 publications

(34 citation statements)

References 26 publications

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“…Furthermore, these cytokines contribute to the development of shock and multiorgan failure (55). MVs are highly stable under the different conditions and environments (56,57). While C. perfringens soluble toxins like PLC also have immunogenicity, stable immunoactive MV could support the infection process (4,55).…”

Section: Discussionmentioning

confidence: 99%

Immunoactive Clostridial Membrane Vesicle Production Is Regulated by a Sporulation Factor

et al. 2017

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Recently, many Gram-positive bacteria as well as Gram-negative bacteria have been reported to produce membrane vesicles (MVs), but little is known regarding the regulators involved in MV formation. We found that a Gram-positive anaerobic pathogen, Clostridium perfringens, produces MVs predominantly containing membrane proteins and cell wall components. These MVs stimulated proinflammatory cytokine production in mouse macrophage-like cells. We suggested that MVs induced interleukin-6 production through the Toll-like receptor 2 (TLR2) signaling pathway. Thus, the MV could have a role in the bacterium-host interaction and bacterial infection pathogenesis. Moreover, we found that the sporulation master regulator gene spo0A was required for vesiculogenesis. A conserved, phosphorylated aspartate residue of Spo0A was indispensable for MV production, suggesting that the phosphorylation of Spo0A triggers MV production. Multiple orphan sensor kinases necessary for sporulation were also required to maximize MV production. These findings imply that C. perfringens actively produces immunoactive MVs in response to the environment changing, as recognized by membrane-spanning sensor kinases and by modulating the phosphorylation level of Spo0A.

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Section: Discussionmentioning

confidence: 99%

Immunoactive Clostridial Membrane Vesicle Production Is Regulated by a Sporulation Factor

et al. 2017

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“…OMVs are nanoscale (∼100 nm) proteoliposomes that constitutively bud from the outer membrane of Gram-negative bacteria (13,14), and they contain components derived from the bacterial outer membrane and periplasm. In contrast to synthetic particulate systems, these OMV vaccines represent a unique system where the antigen and delivery vehicle together are derived from the Neisseria meningitidis pathogen itself (15,16). The proven safety and efficacy records of these OMV vaccines, particularly in The Netherlands (17) and in Norway (12,18), together with the knowledge that vesicles are produced by nearly all species of Gram-negative bacteria (including Escherichia coli), present the possibility of employing OMVs for the delivery of recombinant protein antigens.…”

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confidence: 99%

Delivery of foreign antigens by engineered outer membrane vesicle vaccines

Chen

Osterrieder

Metzger

et al. 2010

Proc. Natl. Acad. Sci. U.S.A.

256

247

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As new disease threats arise and existing pathogens grow resistant to conventional interventions, attention increasingly focuses on the development of vaccines to induce protective immune responses. Given their admirable safety records, protein subunit vaccines are attractive for widespread immunization, but their disadvantages include poor immunogenicity and expensive manufacture. We show here that engineered Escherichia coli outer membrane vesicles (OMVs) are an easily purified vaccine-delivery system capable of greatly enhancing the immunogenicity of a low-immunogenicity protein antigen without added adjuvants. Using green-fluorescent protein (GFP) as the model subunit antigen, genetic fusion of GFP with the bacterial hemolysin ClyA resulted in a chimeric protein that elicited strong anti-GFP antibody titers in immunized mice, whereas immunization with GFP alone did not elicit such titers. Harnessing the specific secretion of ClyA to OMVs, the ClyA-GFP fusion was found localized in OMVs, resulting in engineered recombinant OMVs. The anti-GFP humoral response in mice immunized with the engineered OMV formulations was indistinguishable from the response to the purified ClyA-GFP fusion protein alone and equal to purified proteins absorbed to aluminum hydroxide, a standard adjuvant. In a major improvement over current practice, engineered OMVs containing ClyA-GFP were easily isolated by ultracentrifugation, effectively eliminating the need for laborious antigen purification from cell-culture expression systems. With the diverse collection of heterologous proteins that can be functionally localized with OMVs when fused with ClyA, this work signals the possibility of OMVs as a robust and tunable technology platform for a new generation of prophylactic and therapeutic vaccines.protein subunit | adjuvant

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“…Purified MVs have been shown to elicit a safe and effective means of vaccination against e.g. Neisseria meningitidis Group B infections (Arigita et al 2004).All Flavobacterium psychrophilum strains degrade proteins including gelatine and casein but only some strains degrade elastin (Madsen & Dalsgaard 1998. The ability to degrade elastin has been suggested as a virulence factor for F. psychrophilum, as elastin non-degrading strains (including NCMB1947) show reduced virulence compared to most elastin degrading strains (including 900406-1/3) .…”

mentioning

confidence: 99%

Characterisation of surface blebbing and membrane vesicles produced by Flavobacterium psychrophilum

Møller¹,

Barnes²,

Dalsgaard³

et al. 2005

Dis. Aquat. Org.

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The surface of Flavobacterium psychrophilum was examined by electron microscopy to determine if previous findings of haemagglutination positive (HA+) and haemagglutination negative (HA-) abilities could be correlated with expression of pili or of a capsular layer. A thin capsular layer was observed in both HA+ and HA-strains but typical pili were absent. However, long, tubular blebs that released membrane vesicles (MVs) into the supernatant were observed on up to 94% of cells within 1 sample. The surface blebbing was increased for 1 strain following growth on media with restricted iron availability. The MVs had an intact membrane bilayer and were released from blebbing cells of both strains. The protein profiles of MVs, while containing some banding similarity with the profile of outer membrane preparations (OMPs) and of lysed whole cells (WCs), showed several bands that reacted strongly with rabbit anti-whole-cell antisera. Two distinct bands of approximately 62 and 58 kDA were highly expressed in the MVs and not seen in the OMP. MVs contained proteolytic activity towards gelatine but not towards casein and elastin, which were only degraded by live cells. Low molecular weight lipopolysaccharides (LPS) or lipooligosaccharides (LOS) were associated with the MVs. Only the MVs of the HA+ strain possessed haemagglutinin activity. These findings suggest that the F. psychrophilum may, through surface blebbing, release antigenic MVs that contain some proteolytic activity and may aid the bacterium in releasing nutrients from its surrounding environment as well as playing a role in impeding the immune response of its host. KEY WORDS: Flavobacterium psychrophilum · Membrane vesicles · Surface blebbing · Electron microscopy Resale or republication not permitted without written consent of the publisherDis Aquat Org 64: [201][202][203][204][205][206][207][208][209] 2005 tion positive (HA+) strains and absent on HA-strains (Møller et al. 2003). Lectins and haemagglutinins are often expressed on or in connection with the tip of the long, threadlike surface structures known as pili. Flavobacterium (formerly known as Cytophaga as well as Flexibacter) is generally considered to lack pili expression (Henrichsen & Blom 1975, Pate 1985, McBride 2001 and F. psychrophilum was previously reported to lack pili (Holt et al. 1993, Lorenzen et al. 1997. One member of this group of bacteria, the fish pathogenic agent of bacterial gill disease, Flavobacterium branchiophila (now F. branchiophilum) is, however, reported to possess pili (Heo et al. 1990). A thin, more or less compact slime or capsular layer surrounds F. psychrophilum and may aid in adhesion (Crump et al. 2001). The present study was initiated to determine, by electron microscopy, whether the haemagglutinating ability present in some F. psychrophilum strains was correlated with pili or capsular expression.Several pathogenic Gram-negative bacteria including Escherichia coli O157:H7 (Kolling & Matthews 1999), Pseudomonas aeruginosa (Kadurugamuwa & Beveridge 1995), Nei...

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Stability of mono- and trivalent meningococcal outer membrane vesicle vaccines

Cited by 59 publications

References 26 publications

Immunoactive Clostridial Membrane Vesicle Production Is Regulated by a Sporulation Factor

Immunoactive Clostridial Membrane Vesicle Production Is Regulated by a Sporulation Factor

Delivery of foreign antigens by engineered outer membrane vesicle vaccines

Characterisation of surface blebbing and membrane vesicles produced by Flavobacterium psychrophilum

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