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Outer Membrane Vesicles (Omv) From Neisseria Meningitidis Group B Strain Nz98/254 Measured As Amount Of Total Protein Containing The Pora P1.4 Adsorbed On Aluminium Hydroxide

This article summarizes several clinical trials evaluating meningococcal B vaccines containing outer membrane vesicles (OMV) from Neisseria meningitidis. These vaccines aim to prevent meningococcal disease caused by serogroup B strains. The trials assess the safety, tolerability, and immune responses to different formulations and dosing schedules in various populations, including healthy individuals and those at higher risk of meningococcal disease.

Table of Contents

Introduction

Outer membrane vesicles (OMVs) from Neisseria meningitidis group B are a crucial component in modern meningococcal vaccines. These vaccines aim to protect against meningococcal disease, a serious bacterial infection that can cause meningitis and sepsis. This article will explore the role of OMVs in meningococcal vaccines, their composition, and ongoing research to improve their effectiveness.[1]

What are Outer Membrane Vesicles (OMVs)?

Outer membrane vesicles are small, spherical structures naturally released by many Gram-negative bacteria, including Neisseria meningitidis. These vesicles contain various bacterial proteins and lipids that can stimulate an immune response. In the context of vaccines, OMVs from N. meningitidis group B strain NZ98/254 are used, specifically focusing on the PorA P1.4 protein.[1]

Role of OMVs in Meningococcal Vaccines

OMVs play a critical role in meningococcal vaccines by:

  • Providing a diverse array of antigens to stimulate a broad immune response
  • Enhancing the overall effectiveness of the vaccine against multiple strains of N. meningitidis
  • Helping to overcome the challenge of developing vaccines against serogroup B meningococci, which has been historically difficult due to similarities with human neural antigens

Vaccine Composition and Mechanism

The meningococcal B vaccine (often referred to as Bexsero) contains several components, including:

  • Recombinant NHBA fusion protein: Helps protect against multiple strains of N. meningitidis
  • Recombinant NadA protein: Another important antigen for broad protection
  • Recombinant fHbp fusion protein: Targets a key virulence factor of the bacteria
  • OMVs from N. meningitidis group B strain NZ98/254: Provides additional antigens, particularly PorA P1.4
These components are adsorbed onto aluminum hydroxide, which acts as an adjuvant to enhance the immune response.[1]

The vaccine works by stimulating the production of bactericidal antibodies that recognize and kill meningococcal bacteria. The inclusion of OMVs helps to broaden this immune response, potentially providing protection against a wider range of meningococcal strains.

Clinical Trials and Research

Several clinical trials are ongoing to assess the safety, tolerability, and immunogenicity of meningococcal vaccines containing OMVs:

  • A Phase 2b trial (MENACWY=MEN7B-003) is evaluating different formulations of meningococcal vaccines in healthy infants, including those with OMVs.[2]
  • Another study (SPLEMENGO) is assessing the immunogenicity and safety of three meningococcal B vaccine strategies in adults with asplenia.[3]
  • Research is also being conducted on the use of these vaccines in patients with specific conditions, such as generalized myasthenia gravis.[4]

Safety and Efficacy

Clinical trials have shown that meningococcal vaccines containing OMVs are generally safe and well-tolerated. Common side effects may include:

  • Pain, redness, and swelling at the injection site
  • Fever
  • Irritability in infants
  • Headache and fatigue in older children and adults
Serious adverse events are rare but can occur. The vaccines have demonstrated good efficacy in producing a robust immune response against multiple strains of N. meningitidis group B.[5]

Patient Populations

Meningococcal vaccines containing OMVs are being studied in various patient populations, including:

  • Healthy infants and adolescents
  • Adults with asplenia (absence of a functional spleen)
  • Patients with certain autoimmune conditions
  • Individuals at higher risk of meningococcal disease
These studies aim to determine the optimal vaccination strategies for different age groups and risk factors.[3]

Conclusion

Outer membrane vesicles from Neisseria meningitidis group B are a vital component in modern meningococcal vaccines. Their inclusion helps to provide broader protection against multiple strains of meningococcal bacteria. Ongoing research continues to refine these vaccines, optimizing their safety and efficacy for various patient populations. As our understanding of OMVs and their role in stimulating immune responses grows, we can expect further improvements in meningococcal disease prevention.

Trial Name/Number Vaccine(s) Studied Population Key Objectives
2023-504301-37-00 MenABCWY Healthy participants 11 to <15 years old Assess safety, tolerability, and immunogenicity of different dosing schedules
2023-506449-40-00 MenABCWY-2nd Gen, MenABCWY-1st Gen, MenB, MenACWY-TT Healthy infants 55-89 days old Evaluate safety, reactogenicity, and immune responses to different formulations
2023-508192-36-00 Bexsero Adults 18-60 years old with asplenia Assess immunogenicity and safety compared to healthy controls
2024-513649-35-00 Bexsero, Trumenba Adults 18-75 years old with asplenia Compare immunogenicity and safety of three vaccine strategies

FAQ

  • What is the main component being studied in these meningococcal B vaccine trials? The main component being studied is outer membrane vesicles (OMV) from Neisseria meningitidis group B strain NZ98/254, measured as the amount of total protein containing the PorA P1.4 antigen adsorbed on aluminum hydroxide. This is combined with other recombinant proteins to create multicomponent meningococcal B vaccines.
  • What populations are being studied in these clinical trials? The trials are studying diverse populations including healthy infants, adolescents, and adults, as well as higher-risk groups like individuals with asplenia (lack of a functioning spleen). Ages range from 2 months old to 75 years old across the different studies.
  • What are the main outcomes being measured? The main outcomes being measured are safety/tolerability (e.g. adverse events), immunogenicity (antibody responses measured by serum bactericidal assays), and in some cases efficacy against meningococcal disease. Some trials also assess persistence of immune responses over time.
  • How many doses of vaccine are typically given in these trials? The number of doses varies between studies, but most involve 2-3 doses given over several months. Some trials are comparing different dosing schedules, such as 2 doses vs 3 doses, or different time intervals between doses.
  • Are these vaccines already approved or still experimental? Some of the vaccines, like Bexsero, are already approved and licensed, while others are still experimental formulations being tested. The trials include both studies of approved vaccines in new populations/schedules and studies of novel vaccine candidates.

Ongoing Clinical Trials on Outer Membrane Vesicles (Omv) From Neisseria Meningitidis Group B Strain Nz98/254 Measured As Amount Of Total Protein Containing The Pora P1.4 Adsorbed On Aluminium Hydroxide

  • A study to evaluate the safety of ADX-038 in patients with complement-mediated kidney disease

    Recruiting

    2 1 1 1
    Investigated drugs:
    Italy Spain

  • A study of IM-101 in adults with generalized myasthenia gravis or ocular myasthenia gravis

    Recruiting

    1 1 1
    Investigated drugs:
    Bulgaria Italy Poland Spain

  • Study on Immune Response Differences to Meningococcal Group B Vaccine in Healthy Transgender and Cisgender Adults Aged 18-40

    Recruiting

    3 1 1 1
    Investigated drugs:
    Belgium

  • Study of rMenB+OMV NZ meningococcal group B vaccine immune response and safety in previously vaccinated healthy participants aged 10 to 20 years

    Not recruiting

    3 1 1 1
    Investigated diseases:
    Investigated drugs:
    Finland Italy Spain

  • Study on the Safety and Immune Response of MenABCWY Vaccine and Drug Combination in Healthy Infants with Meningococcal Infections

    Not recruiting

    1 1 1 1
    Investigated drugs:
    Germany Poland Spain

  • Safety and immunogenicity study of Pentavalent Meningococcal ABCYW vaccine (MenPenta SD and MenPenta fHD) compared to licensed meningococcal vaccines in infants, toddlers and children

    Not recruiting

    2 1 1 1
    Investigated drugs:
    Czechia Denmark Finland Germany Poland Spain

  • Study on the Safety and Immune Response of Meningococcal B Vaccine in Adults Without a Spleen

    Not recruiting

    2 1 1 1
    Investigated drugs:
    Austria

  • Study on the Safety and Immune Response of MenABCWY Vaccine in Healthy Adolescents Aged 11-14 with Meningococcal Meningitis

    Not recruiting

    2 1
    Investigated drugs:
    Germany

  • Study on the Safety and Tolerability of DNTH103 for Adults with Generalized Myasthenia Gravis

    Not recruiting

    2 1 1
    Investigated diseases:
    Investigated drugs:
    Czechia Denmark France Italy The Netherlands Norway +3

  • Study on the Safety and Immune Response of Meningococcal B Vaccines in Adults with Asplenia: Bexsero, Trumenba, and a Drug Combination

    Not recruiting

    3 1 1 1
    Investigated diseases:
    Investigated drugs:
    France

Glossary

  • Outer membrane vesicles (OMV): Small bubble-like structures naturally released from the outer membrane of bacteria like Neisseria meningitidis. They contain proteins and other molecules that can stimulate an immune response and are used as components in some meningococcal vaccines.
  • Serogroup B: One of the main disease-causing groups of Neisseria meningitidis bacteria. Vaccines targeting this serogroup have been more challenging to develop compared to other serogroups.
  • PorA P1.4: A specific protein found in the outer membrane of some strains of Neisseria meningitidis. It is one of the antigens included in OMV-based meningococcal B vaccines to help stimulate immunity.
  • Immunogenicity: The ability of a substance, such as a vaccine, to provoke an immune response in the body. In these trials, it is often measured by looking at antibody levels or functional antibody activity against meningococcal bacteria.
  • Serum bactericidal assay (SBA): A laboratory test used to measure functional antibodies that can kill bacteria. In meningococcal vaccine trials, human SBA (hSBA) is often used to assess the immune response to vaccination.
  • Asplenia: The absence of a functioning spleen, either due to surgical removal or impaired function. People with asplenia are at higher risk for certain infections, including meningococcal disease.
  • Adverse event: Any unfavorable and unintended sign, symptom, or disease temporarily associated with the use of a medical treatment or procedure. In vaccine trials, monitoring adverse events is crucial for assessing safety.

References

  1. http://clinicaltrials.eu/trial-id/2023-504301-37-00
  2. http://clinicaltrials.eu/trial-id/2023-506449-40-00
  3. http://clinicaltrials.eu/trial/study-on-the-safety-and-immune-response-of-meningococcal-b-vaccines-in-adults-with-asplenia-bexsero-trumenba-and-a-drug-combination/
  4. http://clinicaltrials.eu/trial/study-on-the-safety-and-tolerability-of-dnth103-for-adults-with-generalized-myasthenia-gravis/
  5. http://clinicaltrials.eu/trial-id/2023-508192-36-00