Identification and optimization of critical process parameters for the production of NOMV vaccine against Neisseria meningitidis

Waterbeemd, Bas van de; Streefland, Mathieu; Keulen, Lonneke van; IJssel, Jan van den; Haan, Alex de; Eppink, M.H.M.; Pol, Leo A. van der

doi:10.1016/j.vaccine.2012.03.028

Cited by 29 publications

(29 citation statements)

References 53 publications

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“…Recent work by our group showed that sOMV release by N. meningitidis increased significantly during the stationary growth phase, but the mechanism was not fully understood [23]. By comparing cysteine repleted with depleted conditions, this study demonstrates that cysteine depletion is the trigger for onset of stationary growth and increased sOMV release (Figure 3).…”

Section: Discussionmentioning

confidence: 63%

“…Previous work demonstrated that vesicle release by N. meningitidis increased during the stationary growth phase [23]. Nutrient analysis of the chemically defined medium indicated that only arginine and cysteine were depleted during early stationary growth.…”

Section: Resultsmentioning

confidence: 92%

“…Previous work showed that vesicle release by N. meningitidis increased during the stationary growth phase [23]. To identify the growth-limiting medium component of these experimental conditions, nutrient consumption was monitored.…”

Section: Resultsmentioning

confidence: 99%

“…The sOMV are released by the bacterium during in vitro growth, without any treatments to enhance vesiculation [21], [22]. The second type, eOMV (extracted OMV, also referred to as native OMV) [15], [17], [23]), uses detergent-free extraction with ethylene-diamine-tetraacetic acid (EDTA) to chelate calcium and magnesium ions. This destabilizes the outer membrane which enhances eOMV release and preserves the desired biochemical and immunological properties, even though eOMV are not fully identical to sOMV [11], [24], [25], [26], [27].…”

Section: Introductionmentioning

confidence: 99%

“…For E. coli these stimuli include heat shock, activitation of the envelope stress response pathway or lysine depletion [31], [32], [33], [34]. Such external triggers have not been identified for N. meningitidis but recent work indicated that vesicle yield increased significantly during stationary growth [23].…”

Section: Introductionmentioning

confidence: 99%

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Cysteine Depletion Causes Oxidative Stress and Triggers Outer Membrane Vesicle Release by Neisseria meningitidis; Implications for Vaccine Development

et al. 2013

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Outer membrane vesicles (OMV) contain immunogenic proteins and contribute to in vivo survival and virulence of bacterial pathogens. The first OMV vaccines successfully stopped Neisseria meningitidis serogroup B outbreaks but required detergent-extraction for endotoxin removal. Current vaccines use attenuated endotoxin, to preserve immunological properties and allow a detergent-free process. The preferred process is based on spontaneously released OMV (sOMV), which are most similar to in vivo vesicles and easier to purify. The release mechanism however is poorly understood resulting in low yield. This study with N. meningitidis demonstrates that an external stimulus, cysteine depletion, can trigger growth arrest and sOMV release in sufficient quantities for vaccine production (±1500 human doses per liter cultivation). Transcriptome analysis suggests that cysteine depletion impairs iron-sulfur protein assembly and causes oxidative stress. Involvement of oxidative stress is confirmed by showing that addition of reactive oxygen species during cysteine-rich growth also triggers vesiculation. The sOMV in this study are similar to vesicles from natural infection, therefore cysteine-dependent vesiculation is likely to be relevant for the in vivo pathogenesis of N. meningitidis.

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Section: Discussionmentioning

confidence: 63%

Section: Resultsmentioning

confidence: 92%

Section: Resultsmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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Cysteine Depletion Causes Oxidative Stress and Triggers Outer Membrane Vesicle Release by Neisseria meningitidis; Implications for Vaccine Development

et al. 2013

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Outer membrane vesicles as platform vaccine technology

Pol

Stork

Ley

2015

Biotechnology Journal

281

241

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Outer membrane vesicles (OMVs) are released spontaneously during growth by many Gram‐negative bacteria. They present a range of surface antigens in a native conformation and have natural properties like immunogenicity, self‐adjuvation and uptake by immune cells which make them attractive for application as vaccines against pathogenic bacteria. In particular with Neisseria meningitidis, they have been investigated extensively and an OMV‐containing meningococcal vaccine has recently been approved by regulatory agencies. Genetic engineering of the OMV‐producing bacteria can be used to improve and expand their usefulness as vaccines. Recent work on meningitis B vaccines shows that OMVs can be modified, such as for lipopolysaccharide reactogenicity, to yield an OMV product that is safe and effective. The overexpression of crucial antigens or simultaneous expression of multiple antigenic variants as well as the expression of heterologous antigens enable expansion of their range of applications. In addition, modifications may increase the yield of OMV production and can be combined with specific production processes to obtain high amounts of well‐defined, stable and uniform OMV particle vaccine products. Further improvement can facilitate the development of OMVs as platform vaccine product for multiple applications.

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Production and purification of bacterial membrane vesicles for biotechnology applications: Challenges and opportunities

2022

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Bacterial membrane vesicles (BMVs) are bi‐layered nanostructures derived from Gram‐negative and Gram‐positive bacteria. Among other pathophysiological roles, BMVs are critical messengers in intercellular communication. As a result, BMVs are emerging as a promising technology for the development of numerous therapeutic applications. Despite the remarkable progress in unveiling BMV biology and functions in recent years, their successful isolation and purification have been limited. Several challenges related to vesicle purity, yield, and scalability severely hamper the further development of BMVs for biotechnology and clinical applications. This review focuses on the current technologies and methodologies used in BMV production and purification, such as ultracentrifugation, density‐gradient centrifugation, size‐exclusion chromatography, ultrafiltration, and precipitation. We also discuss the current challenges related to BMV isolation, large‐scale production, storage, and stability that limit their application. More importantly, the present work explains the most recent strategies proposed for overcoming those challenges. Finally, we summarize the ongoing applications of BMVs in the biotechnological field.

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Identification and optimization of critical process parameters for the production of NOMV vaccine against Neisseria meningitidis

Cited by 29 publications

References 53 publications

Cysteine Depletion Causes Oxidative Stress and Triggers Outer Membrane Vesicle Release by Neisseria meningitidis; Implications for Vaccine Development

Cysteine Depletion Causes Oxidative Stress and Triggers Outer Membrane Vesicle Release by Neisseria meningitidis; Implications for Vaccine Development

Outer membrane vesicles as platform vaccine technology

Production and purification of bacterial membrane vesicles for biotechnology applications: Challenges and opportunities

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