A combined vaccine approach against Vibrio cholerae and ETEC based on outer membrane vesicles

Leitner, Deborah R.; Lichtenegger, Sabine; Temel, Philipp; Zingl, Franz G.; Ratzberger, Desiree; Roier, Sandro; Schild-Prüfert, Kristina; Feichter, Sandra; Reidl, Joachim; Schild, Stefan

doi:10.3389/fmicb.2015.00823

Cited by 58 publications

(67 citation statements)

References 77 publications

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“…Immunogenicity of OMVs has been a subject of an experimental vaccine and has culminated in many promising results against a number of bacterial infections (Acevedo et al, 2014;Asensio et al, 2011;Gaillard et al, 2014;Leitner et al, 2015;Mitra et al, 2016;Norheim et al, 2015;Park et al, 2011;Price et al, 2016;Roberts et al, 2008;van der Pol et al, 2015). Small size, immunogenic properties, and nonreplicative behavior of OMVs make them a good choice for vaccination.…”

Section: Host Immune-modulation By Omvs and Its Potential Applicationmentioning

confidence: 99%

Bacterial outer membrane vesicles: New insights and applications

Anand

Chaudhuri

2016

Molecular Membrane Biology

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Outer membrane vesicles (OMVs) (∼50-250 nm in diameter) are produced by both pathogenic and nonpathogenic bacteria as a canonical end product of secretion. In this review, we focus on the OMVs produced by gram-negative bacteria. We provide an overview of the OMV structure, various factors regulating their production, and their role in modulating host immune response using a few representative examples. In light of the importance of the diverse cargoes carried by OMVs, we discuss the different modes of their entry into the host cell and advances in the high-throughput detection of these OMVs. A conspicuous application of OMVs lies in the field of vaccination; we discuss its success in immunization against human diseases such as pertussis, meningitis, shigellosis and aqua-farming endangering diseases like edwardsiellosis.

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Section: Host Immune-modulation By Omvs and Its Potential Applicationmentioning

confidence: 99%

Bacterial outer membrane vesicles: New insights and applications

Anand

Chaudhuri

2016

Molecular Membrane Biology

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“…Strikingly, crossprotection against O1 and O139 was so far only achieved by including serogroup specific LPS in the immunization for all cholera vaccine candidates tested [15][16][17]. Moreover, we were able to expand the current protection model of V. cholerae to enterotoxigenic Escherichia coli (ETEC) by demonstrating that the inhibition of motility via antiFliC antibodies is a relevant protection mechanism of an OMV-based ETEC vaccine candidate [13]. Thus, the proposed model of inhibition of motility might be a common mechanism important for several vaccine candidates against gastrointestinal pathogens.…”

Section: Descriptionmentioning

confidence: 90%

“…For example, we comprehensively characterized OMVs derived from V. cholerae as a new approach for an effective vaccine candidate against cholera [7][8][9][10]13]. As it turns out OMVs exhibit several advantages compared to other vaccines.…”

mentioning

confidence: 99%

A Glimpse on Outer Membrane Vesicles as Vaccine Candidates

Rl¹,

Gz²,

Schild³

2015

J Vaccines Vaccin

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DescriptionRecently it becomes increasingly evident that actively release of membrane-derived vesicles from cellular surfaces is conserved in all domains of life, including eukaryotes, archaea, Gram-positive and Gram-negative bacteria. For the latter case these spherical structures originate from the outer membrane (OM) and are consequently referred to as outer membrane vesicles (OMVs). Notably, all Gramnegative bacteria that have been investigated so far are able to naturally release OMVs [1,2]. Although OMV formation seems to be a common feature of Gram-negative bacteria the knowledge of their biological roles and biogenesis remains very limited. The hypothesized functions range from simple waste dumps to delivery vehicles for virulence factors (e.g. toxins), degradation enzymes (e.g. toxins and proteases), DNA to enable horizontal gene transfer or signaling molecules for intra-and inter-species communication (e.g. quorum sensing signaling molecules) [3,4]. OMVs range from 10-300 nm in diameter and consist mainly of OM components, such as phospholipids, OM proteins, and lipooligosaccharide (LOS) or lipopolysaccharide (LPS). Additionally, OMVs contain periplasmic components, which are trapped in the lumen of OMVs during the vesiculation process [5]. Hence, OMVs are basically non-living facsimiles of the bacterial cell surface, naturally containing multiple native surface-exposed antigens as well as immunostimulatory molecules [1,6]. Based on their aforementioned immunogenic potency and on positive examples of the OMV-derived vaccines against serogroup B Neisseria meningitides, we initiated several projects over the last years to analyze the potential of OMVs derived from human Gram-negative pathogens as vaccine candidates [7][8][9][10][11][12]. This concise communication summarizes our recent findings in the emerging research field of OMVs as vaccine candidates including immunization studies against human gastrointestinal pathogens (e.g. V. cholerae and ETEC) as well as human and veterinarian respiratory tract pathogens (e.g. Pasteurellaceae family members).For example, we comprehensively characterized OMVs derived from V. cholerae as a new approach for an effective vaccine candidate against cholera [7][8][9][10]13]. As it turns out OMVs exhibit several advantages compared to other vaccines. For example, OMVs are highly stable, even at room temperature, and highly immunogenic without requirements of additional adjuvants [7][8][9]. Thus, a cold chain or accessory buffer solutions are unlikely to be required for the OMV vaccine candidate. In addition, OMV donor strains can be genetically modified to secrete altered OMVs. We successfully applied this strategy to isolate OMVs from a LPS acyltransferase mutant strain, demonstrating that reduction of OMV endotoxicity can be achieved without diminishing the immunogenic potential by genetic modification resulting in underacylated lipid A [10]. Overall, we demonstrated the induction of a specific, long-lasting, high-titer, protective immune response upon mucosal immuniz...

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“…However, the molecular mechanism of virulence factor delivery via vesicles has been unclear. In addition to their production during infection, the key role of OMVs in bacterial virulence is supported by their ability to mimic in animal models diseases caused by the parental pathogens (Kim et al, 2011;Shah et al, 2012;Svennerholm et al, 2017), and to induce protective immune responses (Roy et al, 2011;Leitner et al, 2015;Roier et al, 2016;Liu et al, 2017).…”

Section: Omvs As An Alternative Secretion System: Type-0 Secretion Symentioning

confidence: 99%

“…Cellular binding of LT-carrying OMVs leads to their internalization via lipid rafts and caveolin-dependent endocytosis and internalized vesicles accumulate in a non-acidified compartment of the host cell . The pathogenetic role of ETEC OMVs during infection is supported by their increased production in vivo (Ellis and Kuehn, 2010) and by their ability to induce immune responses to OMV-associated LT and other virulence proteins such as autotransporter TibA, EtpA adhesin and a novel extracytoplasmic protein CexE (Table 1) (Roy et al, 2010(Roy et al, , 2011 which protect against ETEC colonization in a mouse model (Roy et al, 2011;Leitner et al, 2015).…”

Section: Omv-mediated Delivery Of Toxins and Other Virulence Factors mentioning

confidence: 99%

Secretion and Delivery of Intestinal Pathogenic Escherichia coli Virulence Factors via Outer Membrane Vesicles

Rueter

Bielaszewska

2020

Front. Cell. Infect. Microbiol.

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Outer membrane vesicles (OMVs) are nanoscale proteoliposomes secreted from the cell envelope of all Gram-negative bacteria. Originally considered as an artifact of the cell wall, OMVs are now recognized as a general secretion system, which serves to improve the fitness of bacteria and facilitate bacterial interactions in polymicrobial communities as well as interactions between the microbe and the host. In general, OMVs are released in increased amounts from pathogenic bacteria and have been found to harbor much of the contents of the parental bacterium. They mainly encompass components of the outer membrane and the periplasm including various virulence factors such as toxins, adhesins, and immunomodulatory molecules. Numerous studies have clearly shown that the delivery of toxins and other virulence factors via OMVs essentially influences their interactions with host cells. Here, we review the OMV-mediated intracellular deployment of toxins and other virulence factors with a special focus on intestinal pathogenic Escherichia coli. Especially, OMVs ubiquitously produced and secreted by enterohemorrhagic E. coli (EHEC) appear as a highly advanced mechanism for secretion and simultaneous, coordinated and direct delivery of bacterial virulence factors into host cells. OMV-associated virulence factors are not only stabilized by the association with OMVs, but can also often target previously unknown target structures and perform novel activities. The toxins are released by OMVs in their active forms and are transported via cell sorting processes to their specific cell compartments, where they can develop their detrimental effects. OMVs can be considered as bacterial "long distance weapons" that attack host tissues and help bacterial pathogens to establish the colonization of their biological niche(s), impair host cell function, and modulate the defense of the host. Thus, OMVs contribute significantly to the virulence of the pathogenic bacteria.

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A combined vaccine approach against Vibrio cholerae and ETEC based on outer membrane vesicles

Cited by 58 publications

References 77 publications

Bacterial outer membrane vesicles: New insights and applications

Bacterial outer membrane vesicles: New insights and applications

A Glimpse on Outer Membrane Vesicles as Vaccine Candidates

Secretion and Delivery of Intestinal Pathogenic Escherichia coli Virulence Factors via Outer Membrane Vesicles

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