Immunogenicity and Safety of Three Doses of a Bivalent (B:4:P1.19,15 and B:4:P1.7-2,4) Meningococcal Outer Membrane Vesicle Vaccine in Healthy Adolescents

ABSTRACT An experimental bivalent meningococcal outer membrane vesicle (OMV) vaccine (B:4:P1.19,15 and B:4:P1.7-2,4) has been developed to provide wide vaccine coverage particularly of the circulating strains in Europe. A randomized, controlled phase II study (study identification number, 710158/002; ClinicalTrials.gov identifier number, NCT00137917) to evaluate the immunogenicity and safety of three doses of the OMV vaccine when given to healthy 12- to 18-year-olds on a 0-2-4 month (n = 162) or 0-1-6 month schedule (n = 159). A control group received two doses of hepatitis A and one of conjugated meningococcal serogroup C vaccine on a 0-1-6 month schedule (n = 157). Immune response, defined as a fourfold increase in serum bactericidal titer using a range of vaccine-homologous or PorA-related and heterologous strains, was determined for samples taken before and 1 month after vaccination; assays were performed at two laboratories. As measured at the GlaxoSmithKline (GSK) laboratory, the OMV vaccine induced an immune response against homologous or PorA-related strains (in at least 51% of subjects against strains of serosubtype P1.19,15 and at least 66% against strains of serosubtype P1.7-2,4) and against a set of three heterologous strains (in 28% to 46% of subjects). Both laboratories showed consistent results for immune response rates. The OMV vaccine had a similar reactogenicity profile for each schedule. Pain preventing normal activities occurred in approximately one-fifth of the subjects; this was significantly higher than in the control group. The immune responses induced by the bivalent OMV vaccine demonstrated the induction of bactericidal antibodies against the vaccine-homologous/PorA-related strains but also against heterologous strains, indicating the presence of protective antigens in OMVs and confirming the potential of clinical cross-protection.

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Cross-Reactivity of Antibodies against PorA after Vaccination with a Meningococcal B Outer Membrane Vesicle Vaccine

Infection and Immunity ◽

10.1128/iai.71.4.1650-1655.2003 ◽

2003 ◽

Vol 71 (4) ◽

pp. 1650-1655 ◽

Cited By ~ 32

Author(s):

C. L. Vermont ◽

H. H. van Dijken ◽

A. J. Kuipers ◽

C. J. P. van Limpt ◽

W. C. M. Keijzers ◽

...

Keyword(s):

Outer Membrane ◽

Vaccine Strain ◽

Vaccine Coverage ◽

Membrane Vesicle ◽

Geometric Mean ◽

Cross Reactivity ◽

Outer Membrane Vesicle ◽

Specific Antibodies ◽

Fourfold Increase ◽

The Cross

ABSTRACT The cross-reactivity of PorA-specific antibodies induced by a monovalent P1.7-2,4 (MonoMen) and/or a hexavalent (HexaMen) meningococcal B outer membrane vesicle vaccine (OMV) in toddlers and school children was studied by serum bactericidal assays (SBA). First, isogenic vaccine strains and PorA-identical patient isolates were compared as a target in SBA, to ensure that the vaccine strains are representative for patient isolates. Geometric mean titers (GMTs) in SBA against patient isolates with subtypes P1.5-2,10 and P1.5-1,2-2 after vaccination with HexaMen were generally lower than those against vaccine strains with the same subtype, although the percentage of vaccine responders (≥4-fold increase in SBA after vaccination) was not affected. Using various P1.7-2,4 patient isolates, GMTs as well as the number of vaccine responders were higher than for the P1.7-2,4 vaccine strain, indicating that the use of the P1.7-2,4 vaccine strain may have underestimated the immunogenicity of this subtype in HexaMen. Secondly, the cross-reactivity of antibodies induced by MonoMen and HexaMen was studied using several patient isolates that differed from the vaccine subtypes by having minor antigenic variants of one variable region (VR), by having a completely different VR or by having a different combination of VRs. MonoMen induced P1.4-specific antibodies that were cross-reactive with P1.4 variants P1.4-1 and P1.4-3. HexaMen induced a broader cross-reactive antibody response against various patient isolates with one VR identical to a vaccine subtype or a combination of VRs included in HexaMen. Cross-reactivity, measured by a fourfold increase in SBA after vaccination, against these strains ranged from 23 to 92% depending on the subtype of the tested strain and was directed against both VR1 and VR2. The extended cross-reactivity of vaccinee sera induced by HexaMen against antigenic variants has important favorable implications for meningococcal B OMV vaccine coverage.

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Pretreatment of outer membrane vesicle and subsequent infection with influenza virus induces a long-lasting adaptive immune response against broad subtypes of influenza virus

Microbes and Infection ◽

10.1016/j.micinf.2021.104878 ◽

2021 ◽

pp. 104878

Author(s):

Chang-Ung Kim ◽

Sukyeong Eo ◽

Pureum Lee ◽

Sang-Hyun Kim ◽

Young Sang Kim ◽

...

Keyword(s):

Immune Response ◽

Influenza Virus ◽

Outer Membrane ◽

Membrane Vesicle ◽

Adaptive Immune Response ◽

Outer Membrane Vesicle ◽

Subsequent Infection ◽

Adaptive Immune

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Outer membrane vesicle vaccines made from short-chain lipopolysaccharide mutants of serogroup B Neisseria meningitidis: effect of the carbohydrate chain length on the immune response

Vaccine ◽

10.1016/s0264-410x(97)00030-3 ◽

1997 ◽

Vol 15 (11) ◽

pp. 1225-1234 ◽

Cited By ~ 14

Author(s):

S ANDERSEN

Keyword(s):

Immune Response ◽

Neisseria Meningitidis ◽

Outer Membrane ◽

Chain Length ◽

Membrane Vesicle ◽

Carbohydrate Chain ◽

Short Chain ◽

Outer Membrane Vesicle

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Evolution of immune response against Neisseria meningitidis B:14:P1.7,16 before and after the outer membrane vesicle vaccine MenBvac

Vaccine ◽

10.1016/j.vaccine.2012.05.051 ◽

2012 ◽

Vol 30 (34) ◽

pp. 5059-5062 ◽

Cited By ~ 15

Author(s):

François Caron ◽

Valérie Delbos ◽

Estelle Houivet ◽

Ala-Eddine Deghmane ◽

Jean-Philippe Leroy ◽

...

Keyword(s):

Immune Response ◽

Neisseria Meningitidis ◽

Outer Membrane ◽

Membrane Vesicle ◽

Outer Membrane Vesicle ◽

Before And After

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Faculty Opinions recommendation of Meningococcal Outer Membrane Vesicle Composition-Dependent Activation of the Innate Immune Response.

Faculty Opinions – Post-Publication Peer Review of the Biomedical Literature ◽

10.3410/f.726603329.793534933 ◽

2017 ◽

Author(s):

Robert Ernst

Keyword(s):

Immune Response ◽

Outer Membrane ◽

Innate Immune Response ◽

Membrane Vesicle ◽

Innate Immune ◽

Outer Membrane Vesicle

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Combined Administration of Meningococcal Serogroup B Outer Membrane Vesicle Vaccine and Conjugated Serogroup C Vaccine Indicated for Prevention of Meningococcal Disease Is Safe and Immunogenic

Clinical and Diagnostic Laboratory Immunology ◽

10.1128/cdli.12.5.599-605.2005 ◽

2005 ◽

Vol 12 (5) ◽

pp. 599-605 ◽

Cited By ~ 5

Author(s):

Ingeborg S. Aaberge ◽

Philipp Oster ◽

Oddveig S. Helland ◽

Anne-Cathrine Kristoffersen ◽

Ellen Ypma ◽

...

Keyword(s):

Immune Responses ◽

Outer Membrane ◽

Meningococcal Disease ◽

Membrane Vesicle ◽

Enzyme Linked Immunosorbent Assay ◽

Outer Membrane Vesicle ◽

Active Components ◽

Serious Adverse Events ◽

Group B ◽

Combined Vaccine

ABSTRACT MenBvac and Menjugate are safe and efficacious vaccines. The purpose of this study was to evaluate safety and immunogenicity of the combination (MenB/C) of the lyophilized active components of the conjugated group C vaccine Menjugate when reconstituted with the full liquid group B outer membrane vesicle vaccine MenBvac compared to MenBvac and Menjugate given separately. At 6-week intervals, healthy adults were given one dose of MenB/C followed by two doses of MenBvac (MenB/C group), three doses of MenBvac (MenB group), or one dose of Menjugate and two doses of placebo (MenC group). Injection site reactions were frequent in all groups. However, most reactions were short lasting and mild or moderate in intensity, and the vaccines were found to be well tolerated, with no vaccine-related serious adverse events. MenB/C was immunogenic with regard to both serogroup B and C meningococci. Both the serum bactericidal assay and the enzyme-linked immunosorbent assay analyses showed that the immune responses of the combination vaccine were similar to the immune responses of its separate components MenBvac and Menjugate for both serogroup B and C. In conclusion, the combined MenB/C vaccine is safe and immunogenic. The two vaccines do not interact negatively with each other and can easily be administered in the same syringe. The induced immune responses suggest that the combined vaccine is likely to confer protection against systemic group B disease caused by the vaccine strain as well as against group C meningococcal disease.

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