scholarly journals Neisseria lactamica Protects against Experimental Meningococcal Infection

2002 ◽  
Vol 70 (7) ◽  
pp. 3621-3626 ◽  
Author(s):  
Kerry J. Oliver ◽  
Karen M. Reddin ◽  
Philippa Bracegirdle ◽  
Michael J. Hudson ◽  
Ray Borrow ◽  
...  
Keyword(s):  
Outer Membrane ◽  
Meningococcal Disease ◽  
Membrane Vesicles ◽  
Outer Membrane Vesicles ◽  
Meningococcal Infection ◽  
Natural Immunity ◽  
Lethal Challenge ◽  
Diverse Range ◽  
Whole Cells ◽  
Bacteremic Infection

ABSTRACT Immunological and epidemiological evidence suggests that the development of natural immunity to meningococcal disease results from colonization of the nasopharynx by commensal Neisseria spp., particularly with N. lactamica. We report here that immunization with N. lactamica killed whole cells, outer membrane vesicles, or outer membrane protein (OMP) pools and protected mice against lethal challenge by a number of diverse serogroup B and C meningococcal isolates in a model of bacteremic infection. Sera raised to N. lactamica killed whole cells, OMPs, or protein pools were found to cross-react with meningococcal isolates of a diverse range of genotypes and phenotypes. The results confirm the potential of N. lactamica to form the basis of a vaccine against meningococcal disease.

scholarly journals Phase I Safety and Immunogenicity Study of a Candidate Meningococcal Disease Vaccine Based on Neisseria lactamica Outer Membrane Vesicles

2009 ◽  
Vol 16 (8) ◽  
pp. 1113-1120 ◽  
Author(s):  
Andrew R. Gorringe ◽  
Stephen Taylor ◽  
Charlotte Brookes ◽  
Mary Matheson ◽  
Michelle Finney ◽  
...  
Keyword(s):  
Phase I ◽  
Outer Membrane ◽  
Meningococcal Disease ◽  
Membrane Vesicles ◽  
Outer Membrane Vesicles ◽  
Enzyme Linked Immunosorbent Assay ◽  
Natural Immunity ◽  
Lethal Challenge ◽  
Humoral Immune ◽  
Neisseria Lactamica

ABSTRACT Natural immunity to meningococcal disease in young children is associated epidemiologically with carriage of commensal Neisseria species, including Neisseria lactamica. We have previously demonstrated that outer membrane vesicles (OMVs) from N. lactamica provide protection against lethal challenge in a mouse model of meningococcal septicemia. We evaluated the safety and immunogenicity of an N. lactamica OMV vaccine in a phase I placebo-controlled, double-blinded clinical trial. Ninety-seven healthy young adult male volunteers were randomized to receive three doses of either an OMV vaccine or an Alhydrogel control. Subsequently, some subjects who had received the OMV vaccine also received a fourth dose of OMV vaccine, 6 months after the third dose. Injection site reactions were more frequent in the OMV-receiving group, but all reactions were mild or moderate in intensity. The OMV vaccine was immunogenic, eliciting rises in titers of immunoglobulin G (IgG) against the vaccine OMVs, together with a significant booster response, as determined by an enzyme-linked immunosorbent assay. Additionally, the vaccine induced modest cross-reactive immunity to six diverse strains of serogroup B Neisseria meningitidis, including IgG against meningococcal OMVs, serum bactericidal antibodies, and opsonophagocytic activity. The percentages of subjects showing ≥4-fold rises in bactericidal antibody titer obtained were similar to those previously reported for the Norwegian meningococcal OMV vaccine against the same heterologous meningococcal strain panel. In conclusion, this N. lactamica OMV vaccine is safe and induces a weak but broad humoral immune response to N. meningitidis.

scholarly journals Expression of Heterologous Antigens in Commensal Neisseria spp.: Preservation of Conformational Epitopes with Vaccine Potential

2004 ◽  
Vol 72 (11) ◽  
pp. 6511-6518 ◽  
Author(s):  
Clíona A. O'Dwyer ◽  
Karen Reddin ◽  
Denis Martin ◽  
Stephen C. Taylor ◽  
Andrew R. Gorringe ◽  
...  
Keyword(s):  
Membrane Protein ◽  
Outer Membrane ◽  
Meningococcal Disease ◽  
Protective Efficacy ◽  
Membrane Vesicles ◽  
Outer Membrane Vesicles ◽  
Heterologous Proteins ◽  
Protein Vaccine ◽  
Native Conformation ◽  
Protein Antigens

ABSTRACT Commensal neisseriae share with Neisseria meningitidis (meningococcus) a tendency towards overproduction of the bacterial outer envelope, leading to the formation and release during growth of outer membrane vesicles (OMVs). OMVs from both meningococci and commensal neisseriae have shown promise as vaccines to protect against meningococcal disease. We report here the successful expression at high levels of heterologous proteins in commensal neisseriae and the display, in its native conformation, of one meningococcal outer membrane protein vaccine candidate, NspA, in OMVs prepared from such a recombinant Neisseria flavescens strain. These NspA-containing OMVs conferred protection against otherwise lethal intraperitoneal challenge of mice with N. meningitidis serogroup B, and sera raised against them mediated opsonophagocytosis of meningococcal strains expressing this antigen. This development promises to facilitate the design of novel vaccines containing membrane protein antigens that are otherwise difficult to present in native conformation that provide cross-protective efficacy in the prevention of meningococcal disease.

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.

The development of a meningococcal disease vaccine based on outer membrane vesicles

Vaccine ◽  
2005 ◽  
Vol 23 (17-18) ◽  
pp. 2210-2213 ◽  
Author(s):  
A GORRINGE ◽  
D HALLIWELL ◽  
M MATHESON ◽  
K REDDIN ◽  
M FINNEY ◽  
...  
Keyword(s):  
Outer Membrane ◽  
Meningococcal Disease ◽  
Membrane Vesicles ◽  
Outer Membrane Vesicles

Serotypes and subtypes of Neisseria meningitidis serogroup B strains associated with meningococcal disease in Canada, 1977–1989

1991 ◽  
Vol 37 (8) ◽  
pp. 613-617 ◽  
Author(s):  
F. E. Ashton ◽  
L. Mancino ◽  
A. J. Ryan ◽  
J. T. Poolman ◽  
H. Abdillahi ◽  
...  
Keyword(s):  
Monoclonal Antibodies ◽  
Neisseria Meningitidis ◽  
Key Words ◽  
Outer Membrane ◽  
Meningococcal Disease ◽  
Membrane Vesicles ◽  
Outer Membrane Vesicles ◽  
Whole Cell ◽  
Immunosorbent Assays ◽  
Cell Elisa

Typing of Neisseria meningitidis serogroup B disease isolates was carried out using a panel of serotype- and subtype-specific monoclonal antibodies (MAbs) in enzyme-linked immunosorbent assays (ELISA). Three hundred and sixty-two strains isolated from 1977 to 1986 were typed using five serotyping and seven subtyping reagents and outer membrane vesicles as antigens. Serotype 2b accounted for 30% of the disease isolates. The most common subtype was P1.2, which occurred on 18.5% of all strains or 48.6% of the serotype 2b strains. Of the 362 strains typed, 135 (37.3%) were serotyped and 122 (33.7%) were subtyped. Overall, 185 (51.1%) of the strains could be assigned a serotype and (or) subtype. Strains (221) isolated during the years 1987–1989 were typed using a panel of 6 serotyping and 12 subtyping reagents by whole-cell ELISA. Strains of serotypes 4 (21.7%) and 15 (20.8%) were the most common and carried a wide variety of subtypes. The most common subtypes were P1.2 (11.8%) and P1.16 (9.5%). Of the 221 strains analyzed, 132 (59.7%) were assigned a serotype and 123 (55.7%) a subtype and with all 18 MAbs, 192 (86.9%) of the strains were serotyped and (or) subtyped. Two different MAbs to the four epitopes 2a, 15, P1.2, and P1.16 gave discordant reactions of 0.3, 6.6, 2.6, and 2.2%, respectively, when used to analyze over 300 strains of N. meningitidis. Key words: meningococcal serotypes, subtypes.

Outer membrane vesicles extracted from Neisseria meningitidis serogroup X for prevention of meningococcal disease in Africa

2017 ◽  
Vol 121 ◽  
pp. 194-201 ◽  
Author(s):  
Reinaldo Acevedo ◽  
Caridad Zayas ◽  
Gunnstein Norheim ◽  
Sonsire Fernández ◽  
Barbara Cedré ◽  
...  
Keyword(s):  
Neisseria Meningitidis ◽  
Outer Membrane ◽  
Meningococcal Disease ◽  
Membrane Vesicles ◽  
Outer Membrane Vesicles

Electrophysiological Characterization of Transport Across Outer Membrane Channels from Gram-Negative Bacteria in Their Native Environment

2019 ◽  
Author(s):  
Jiajun Wang ◽  
Rémi Terrasse ◽  
Jayesh Arun Bafna ◽  
Lorraine Benier ◽  
Mathias Winterhalter
Keyword(s):  
Outer Membrane ◽  
Lipid Membrane ◽  
Membrane Vesicles ◽  
Outer Membrane Vesicles ◽  
Multi Drug Resistance ◽  
Gram Negative Bacteria ◽  
Membrane Channels ◽  
Gram Negative ◽  
Electrophysiological Characterization

Multi-drug resistance in Gram-negative bacteria is often associated with low permeability of the outer membrane. To investigate the role of membrane channels in the uptake of antibiotics, we extract, purify and reconstitute them into artificial planar membranes. To avoid this time-consuming procedure, here we show a robust approach using fusion of native outer membrane vesicles (OMV) into planar lipid bilayer which moreover allows also to some extend the characterization of membrane protein channels in their native environment. Two major membrane channels from <i>Escherichia coli</i>, OmpF and OmpC, were overexpressed from the host and the corresponding OMVs were collected. Each OMV fusion revealed surprisingly single or only few channel activities. The asymmetry of the OMV´s translates after fusion into the lipid membrane with the LPS dominantly present at the side of OMV addition. Compared to conventional reconstitution methods, the channels fused from OMVs containing LPS have similar conductance but a much broader distribution. The addition of Enrofloxacin on the LPS side yields somewhat higher association (<i>k<sub>on</sub></i>) and lower dissociation (<i>k<sub>off</sub></i>) rates compared to LPS-free reconstitution. We conclude that using outer membrane vesicles is a fast and easy approach for functional and structural studies of membrane channels in the native membrane.

Sign in / Sign up

Export Citation Format

Share Document