scholarly journals Cross-reactivity with Brazilian strains of Neisseria meningitidis B after immunization with outer membrane vesicles

2019 ◽  
Vol 7 ◽  
pp. 251513551989482
Author(s):  
Gabriela Trzewikoswki de Lima ◽  
Amanda Izeli Portilho ◽  
Elizabeth De Gaspari
Keyword(s):  
Public Health ◽  
Neisseria Meningitidis ◽  
Outer Membrane ◽  
Immunosorbent Assay ◽  
Humoral Response ◽  
Membrane Vesicles ◽  
Cross Reactivity ◽  
Outer Membrane Vesicles ◽  
Antigen Recognition ◽  
Enzyme Linked Immunosorbent Assay

Background: Immunization against Neisseria meningitidis is important for public health. Vaccines composed of cross-reactivity antigens avoid strain-specific responses, ensuring more comprehensive protection. Methods: The cross-reactivity between three strains from the last outbreak of N. meningitidis in Brazil was assessed in our studies, using enzyme-linked immunosorbent assay (ELISA) and immunoblotting assays. Results: Both assays verifed a similar humoral response between the strains evaluated. Patterns of antigen recognition differed with each dose evaluated. Conclusions: We observed that immunization with N. meningitidis B outer membrane vesicles (OMVs) led to the production of antibodies that recognized antigens of heterologous strains, indicating possible protection against these evaluated strains.

scholarly journals New strategy to select cross-reactivity Meningococci strains: immunization with Outer membrane vesicles of serogroup C and cationic lipid as adjuvant

2021 ◽  
Author(s):  
Amanda Izeli Portilho ◽  
Gabriela Trzewikowski de Lima ◽  
Elizabeth De Gaspari
Keyword(s):  
Outer Membrane ◽  
Public Health Problem ◽  
Cationic Lipid ◽  
Humoral Response ◽  
Membrane Vesicles ◽  
Cross Reactivity ◽  
Outer Membrane Vesicles ◽  
High Avidity ◽  
Avidity Index ◽  
High Avidity Index

Background: Invasive meningococcal disease (IMD), caused by Neisseria meningitidis, is a public health problem, associated with high levels of morbidity and mortality, capable of causing outbreaks or epidemics, but preventable through vaccination. In Brazil, the main serogroups isolated are C and B. The last epidemic occurred in the 80s, in Sao Paulo, because of a B:4:P1.15 strain. Methods: Adult Swiss mice were immunized with outer membrane vesicles (OMV) of N. meningitidis strain C:4:P1.15, adjuvanted by the cationic lipid dioctadecyldimethylammonium bromide in bilayer fragments (DDA-BF), administered via prime-booster (intranasal/subcutaneous) scheme. The humoral response was accessed by Immunoblotting and ELISA, using homologous immunization strain and a different serogroup but equal serosubtype strain, N. meningitidis B:4:P1.15. Results: Immunoblotting revealed the recognition of antigens associated with the molecular weight of Porin A and Opacity proteins, which are immunogenic but highly heterogeneous, and Tbp and NspA, which are more homogeneous between meningococci strains. ELISA results showed antibody production that persisted after 190 days and recognized the C:4:P1.15 and the B:4:P1.15 strains, with high avidity index. The adjuvanted group recognized antigens following the IN prime and had a higher avidity index against the heterologous strain. Conclusions: DDA-BF improved the humoral response, but the OMV alone induced high avidity index antibodies as well. Even though these are preliminary results, we see it as a promising approach for affordable meningococcal immunization in developing countries, at outbreak or epidemic situations.

scholarly journals Impact of Reducing Complement Inhibitor Binding on the Immunogenicity of Native Neisseria meningitidis Outer Membrane Vesicles

PLoS ONE ◽  
2016 ◽  
Vol 11 (2) ◽  
pp. e0148840 ◽  
Author(s):  
Helene Daniels-Treffandier ◽  
Karlijn de Nie ◽  
Leanne Marsay ◽  
Christina Dold ◽  
Manish Sadarangani ◽  
...  
Keyword(s):  
Neisseria Meningitidis ◽  
Outer Membrane ◽  
Membrane Vesicles ◽  
Outer Membrane Vesicles ◽  
Complement Inhibitor ◽  
Inhibitor Binding

scholarly journals Immunogenicity of Intranasally Administered Meningococcal Native Outer Membrane Vesicles in Mice

1999 ◽  
Vol 67 (1) ◽  
pp. 113-119 ◽  
Author(s):  
Nancy B. Saunders ◽  
David R. Shoemaker ◽  
Brenda L. Brandt ◽  
E. Ellen Moran ◽  
Thomas Larsen ◽  
...  
Keyword(s):  
Immune Response ◽  
Antibody Response ◽  
Outer Membrane ◽  
Membrane Vesicles ◽  
Lavage Fluid ◽  
Lung Lavage ◽  
Outer Membrane Vesicles ◽  
Enzyme Linked Immunosorbent Assay ◽  
Natural Immunity ◽  
Bactericidal Antibody

ABSTRACT Colonization of the human nasopharyngeal region by Neisseria meningitidis is believed to lead to natural immunity. Although the presence of bactericidal antibody in serum has been correlated with immunity to meningococcal disease, mucosal immunity at the portal of entry may also play an important role. This study was undertaken to examine in mice the possibility of safely using native outer membrane vesicles (NOMV) not exposed to detergent as an intranasal (i.n.) vaccine. The mucosal and systemic responses of mice to intranasal and intraperitoneal (i.p.) vaccination with NOMV were compared over a range of doses from 0.1 to 20 μg. Intranasal vaccination of mice with NOMV induced a strong systemic bactericidal antibody response, as well as a strong local immunoglobulin A immune response in the lung as determined by assay of lung lavage fluid by enzyme-linked immunosorbent assay and lung antibody secreting cells by enzyme-linked immunospot assay. However, 8- to 10-fold-higher doses of NOMV were required i.n. compared to i.p. to elicit an equivalent bactericidal antibody response in serum. Some NOMV vaccine was aspirated into the lungs of mice during i.n. immunization and resulted in an acute inflammatory response that peaked at 1 to 2 days postimmunization and was cleared by day 7. These results indicate that i.n. delivery of meningococcal NOMV in mice is highly effective in eliciting the production of both a mucosal immune response and a systemic bactericidal antibody response.

scholarly journals Sulfate depletion triggers overproduction of phospholipids and the release of outer membrane vesicles by Neisseria meningitidis

2019 ◽  
Vol 9 (1) ◽  
Author(s):  
Matthias J. H. Gerritzen ◽  
Dirk E. Martens ◽  
Joost P. Uittenbogaard ◽  
René H. Wijffels ◽  
Michiel Stork
Keyword(s):  
Neisseria Meningitidis ◽  
Outer Membrane ◽  
Membrane Vesicles ◽  
Outer Membrane Vesicles ◽  
Sulfate Depletion

scholarly journals Continuous production of Neisseria meningitidis outer membrane vesicles

2019 ◽  
Vol 103 (23-24) ◽  
pp. 9401-9410
Author(s):  
Matthias J.H. Gerritzen ◽  
Lilli Stangowez ◽  
Bas van de Waterbeemd ◽  
Dirk E. Martens ◽  
René H. Wijffels ◽  
...  
Keyword(s):  
Steady State ◽  
Neisseria Meningitidis ◽  
Outer Membrane ◽  
Continuous Production ◽  
Membrane Vesicles ◽  
Outer Membrane Vesicles ◽  
Volumetric Productivity ◽  
Batch Processes ◽  
Capital Costs ◽  
Production Processes

Abstract 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.

scholarly journals Relative Immunogenicity of PorA Subtypes in a Multivalent Neisseria meningitidis Vaccine Is Not Dependent on Presentation Form

2003 ◽  
Vol 71 (11) ◽  
pp. 6367-6371 ◽  
Author(s):  
Thomas A. Luijkx ◽  
Harry van Dijken ◽  
Hendrik-Jan Hamstra ◽  
Betsy Kuipers ◽  
Peter van der Ley ◽  
...  
Keyword(s):  
Neisseria Meningitidis ◽  
Outer Membrane ◽  
Bactericidal Activity ◽  
Immunoglobulin G ◽  
Clinical Studies ◽  
Membrane Vesicles ◽  
Outer Membrane Vesicles ◽  
The Other ◽  
Meningococcal Vaccine ◽  
Serum Bactericidal Activity

ABSTRACT The hexavalent meningococcal vaccine HexaMen, containing six PorAs on two vesicles, was tested in clinical studies. Although fourfold increases in serum bactericidal activity (SBA) titers against all of the PorAs were observed, there were significant differences between PorA-specific SBA titers. SBA titers were mainly directed against one PorA from each vesicle, P1.5-2,10 and P1.5-1,2-2, and were lower against the other PorAs, especially P1.7-2,4 and P1.19,15-1. We investigated whether these differences were due to immunological interference that resulted in competition between the three PorAs on the same vesicle or whether they were caused by a difference in the immunogenicities of the separate PorAs. Therefore, mice were immunized either with HexaMen, with six monovalent outer membrane vesicles (OMVs) representing the same six PorAs simultaneously (HexaMix), or with only one of the monovalent OMVs. The immunoglobulin G and SBA titers after HexaMen immunization in mice resembled the results obtained in clinical studies. Although immunization with HexaMix gave higher titers than immunization with HexaMen for some PorAs, the pattern of high and low titers was the same. Similar differences in immunogenicity between subtypes were seen after monovalent immunization when interference was eliminated as a cause of the differences. Monovalent immunization resulted in higher titers for P1.5-1,2-2 and P1.7,16 than immunization with HexaMen. However, no significant differences were found for the weakly immunogenic PorAs, P1.7-2,4 and P1.19,15-1. Since immunization with the six PorAs in the trivalent presentation form (HexaMen) and in the mixture of monovalent vesicles (HexaMix) resulted in the same pattern of high and low titers, we concluded that the differences between the PorA-specific responses are due to differences in the immunogenicities of the various PorAs and not due to interference that results in competition between different PorAs.

scholarly journals Naturally Produced Outer Membrane Vesicles from Pseudomonas aeruginosa Elicit a Potent Innate Immune Response via Combined Sensing of Both Lipopolysaccharide and Protein Components

2010 ◽  
Vol 78 (9) ◽  
pp. 3822-3831 ◽  
Author(s):  
Terri N. Ellis ◽  
Sara A. Leiman ◽  
Meta J. Kuehn
Keyword(s):  
Pseudomonas Aeruginosa ◽  
Outer Membrane ◽  
Membrane Vesicles ◽  
Outer Membrane Vesicles ◽  
Host Cells ◽  
Enzyme Linked Immunosorbent Assay ◽  
Response Analysis ◽  
Specific Response ◽  
Protein Components ◽  
Vesicle Proteins

ABSTRACT Pseudomonas aeruginosa is a prevalent opportunistic human pathogen that, like other Gram-negative pathogens, secretes outer membrane vesicles. Vesicles are complex entities composed of a subset of envelope lipid and protein components that have been observed to interact with and be internalized by host cells. This study characterized the inflammatory responses to naturally produced P. aeruginosa vesicles and determined the contribution of vesicle Toll-like receptor (TLR) ligands and vesicle proteins to that response. Analysis of macrophage responses to purified vesicles by real-time PCR and enzyme-linked immunosorbent assay identified proinflammatory cytokines upregulated by vesicles. Intact vesicles were shown to elicit a profoundly greater inflammatory response than the response to purified lipopolysaccharide (LPS). Both TLR ligands LPS and flagellin contributed to specific vesicle cytokine responses, whereas the CpG DNA content of vesicles did not. Neutralization of LPS sensing demonstrated that macrophage responses to the protein composition of vesicles required the adjuvantlike activity of LPS to elicit strain specific responses. Protease treatment to remove proteins from the vesicle surface resulted in decreased interleukin-6 and tumor necrosis factor alpha production, indicating that the production of these specific cytokines may be linked to macrophage recognition of vesicle proteins. Confocal microscopy of vesicle uptake by macrophages revealed that vesicle LPS allows for binding to macrophage surfaces, whereas vesicle protein content is required for internalization. These data demonstrate that macrophage sensing of both LPS and protein components of outer membrane vesicles combine to produce a bacterial strain-specific response that is distinct from those triggered by individual, purified vesicle components.

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