Spontaneously released Neisseria meningitidis outer membrane vesicles as vaccine platform: production and purification

Gerritzen, Matthias J.H.; Salverda, Merijn L.M.; Martens, Dirk E.; Wijffels, René H.; Stork, Michiel

doi:10.1016/j.vaccine.2019.01.076

Cited by 46 publications

(40 citation statements)

References 40 publications

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“…OMVs proved to be a flexible vaccine production platform and very complex structures that contain immune stimulators (e.g., LPS, proteins, and DNA) and antigenic molecules delivered to immune-competent cells of the immune system [36,124,159]. Therefore, OMV has an intrinsic adjuvant effect overloaded antigens from bacteria, but also over heterologous antigens that can be incorporated or combined in a single formulation, the immunestimulating properties of the vesicle can be engineered, and the toxicity can be reduced [36,112,124,159]. Moreover, the versatility to enable administration via the mucosal or parenteral route offers a significant choice.…”

Section: Discussionmentioning

confidence: 99%

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Outer Membrane Vesicles (OMVs) Produced by Gram-Negative Bacteria: Structure, Functions, Biogenesis, and Vaccine Application

Furuyama

Sircili

2021

BioMed Research International

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Section: Discussionmentioning

confidence: 99%

“…Moreover, the versatility to enable administration via the mucosal or parenteral route offers a significant choice. The adjuvant potential and increased knowledge in the design of OMV over the last few decades will also enable the future development of the next generation of novel vaccine formulations [36,124,159].…”

Section: Discussionmentioning

confidence: 99%

Outer Membrane Vesicles (OMVs) Produced by Gram-Negative Bacteria: Structure, Functions, Biogenesis, and Vaccine Application

Furuyama

Sircili

2021

BioMed Research International

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“…baumannii nOMV (native OMV) was prepared from bacterial cells cultured in 10 liters of LB broth. The cells were suspended in Buffer (10 mM Tris-HCl, 10 mM EDTA, 150 mM NaCl, pH7.4), 2.5 times wet weight, and incubated at 56 • C for 1 h. After being cooled to 4 • C, the suspension was sheared at 18000 rpm for 5 min in a High-speed dispersator (XHF-D, Ningbo Scientz, China) in an ice bath (19,28). The suspension was centrifuged first at 5,000 × g for 20 min, and then at 30,000× g for 20 min.…”

Section: Preparation Of Abomvsmentioning

confidence: 99%

“…Several methods have been developed to prepare OMVs. Gram-negative bacteria secrete OMVs spontaneously to the culture medium in the process of growth, and OMVs could be enriched and isolated from the cell culture supernatant (19). Other methods to obtain OMVs from bacterial cells included using detergents and/or chelating agents to promote the production of the OMVs (20,21), always with a higher yield than isolation from the culture supernatant (22).…”

Section: Introductionmentioning

confidence: 99%

Development of Different Methods for Preparing Acinetobacter baumannii Outer Membrane Vesicles Vaccine: Impact of Preparation Method on Protective Efficacy

Sun

Chen

et al. 2020

Front. Immunol.

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Acinetobacter baumannii (A. baumannii) is becoming a common global concern due to the emergence of multi-drug or pan-drug resistant strains. Confronting the issue of antimicrobial resistance by developing vaccines against the resistant pathogen is becoming a common strategy. In this study, different methods for preparing A. baumannii outer membrane vesicles (AbOMVs) vaccines were developed. sOMV (spontaneously released AbOMV) was extracted from the culture supernatant, while SuOMV (sucrose-extracted AbOMV) and nOMV (native AbOMV) were prepared from the bacterial cells. Three AbOMVs exhibited significant differences in yield, particle size, protein composition, and LPS/DNA content. To compare the protective efficacy of the three AbOMVs, groups of mice were immunized either intramuscularly or intranasally with each AbOMV. Vaccination via both routes conferred significant protection against lethal and sub-lethal A. baumannii challenge. Moreover, intranasal vaccination provided more robust protection, which may be attributed to the induction of significant sIgA response in mucosal sites. Among the three AbOMVs, SuOMV elicited the highest level of protective immunity against A. baumannii infection, whether intramuscular or intranasal immunization, which was characterized by the expression of the most profound specific serum IgG or mucosal sIgA. Taken together, the preparation method had a significant effect on the yield, morphology, and composition of AbOMVs, that further influenced the protective effect against A. baumannii infection.

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“…Recently, we showed high yields of sOMV from a batch cultivation (Gerritzen et al 2019b). This was reached by using a production strain with reduced linkage of the outer membrane to the peptidoglycan in combination with sulfur source depletion (Gerritzen et al 2019a), and high dissolved oxygen levels (Gerritzen et al 2018).…”

Section: Introductionmentioning

confidence: 99%

Continuous production of Neisseria meningitidis outer membrane vesicles

Gerritzen

Stangowez

Waterbeemd

et al. 2019

Appl Microbiol Biotechnol

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Outer membrane vesicles (OMVs) are nanoparticles secreted by Gram-negative bacteria that can be used for diverse biotechnological applications. Interesting applications have been developed, where OMVs are the basis of drug delivery, enzyme carriers, adjuvants, and vaccines. Historically, OMV research has mainly focused on vaccines. Therefore, current OMV production processes have been based on batch processes. The production of OMVs in batch mode is characterized by relatively low yields and high costs. Transition of OMV production processes from batch to continuous processes could increase the volumetric productivity, reduce the production and capital costs, and result in a higher quality product. Here, we study the continuous production of Neisseria meningitidis OMVs to improve volumetric productivity. Continuous cultivation of N. meningitidis resulted in a steady state with similar high OMV concentrations as are reached in current batch processes. The steady state was reproducible and could be maintained for at least 600 h. The volumetric productivity of a continuous culture reached 4.0 × 1014 OMVs per liter culture per day, based on a dilution rate of 1/day. The tested characteristics of the OMVs did not change during the experiments showing feasibility of a continuous production process for the production of OMVs for any application.Electronic supplementary materialThe online version of this article (10.1007/s00253-019-10163-z) contains supplementary material, which is available to authorized users.

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Spontaneously released Neisseria meningitidis outer membrane vesicles as vaccine platform: production and purification

Cited by 46 publications

References 40 publications

Outer Membrane Vesicles (OMVs) Produced by Gram-Negative Bacteria: Structure, Functions, Biogenesis, and Vaccine Application

Outer Membrane Vesicles (OMVs) Produced by Gram-Negative Bacteria: Structure, Functions, Biogenesis, and Vaccine Application

Development of Different Methods for Preparing Acinetobacter baumannii Outer Membrane Vesicles Vaccine: Impact of Preparation Method on Protective Efficacy

Continuous production of Neisseria meningitidis outer membrane vesicles

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