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Inducing Meningococcal Meningitis Serogroup C in Mice via Intracisternal Delivery
Published on: November 5, 2019
Immunogenicity of various presentation forms of PorA outer membrane protein of Neisseria meningitidis in mice
C C Peeters1, I J Claassen, M Schuller
1Laboratory for Vaccine development and Immune Mechanisms, National Institute of Public Health and Environment, Bilthoven, The Netherlands.
Abstract:
In this study we compare different vaccine formulations containing meningococcal PorA outer membrane protein; purified PorA, outer membrane vesicles (OMV) and immune-stimulating complexes (iscom). Bactericidal antibodies could be generated by the OMV and iscom formulation but not with purified PorA using either A1PO4 or Quil-A as adjuvant. OMV and iscom formulations revealed similar immunogenicity when tested in a dose response manner, with respect to bactericidal as well as OMV-binding antibodies. The anti-OMV IgG subclass response induced by PorA in OMV formulation was found in all subclasses IgG1, IgG2a, IgG2b, IgG3. OMP-iscoms induced very high IgG1 anti-OMV antibodies but almost no IgG3 response. Also, OMP-iscoms appeared to be a potent inducer of antibodies directed against linear peptides corresponding to surface exposed loops of PorA. In addition, iscoms as well as purified PorA with Quil-A as adjuvant (but not with A1PO4) induced high levels of antibodies against purified PorA. In summary, in addition to the OMV formulation, only iscoms containing PorA are able to generate an anamnestic and bactericidal antibody response.
Insights
Outer membrane vesicles (OMV) and immune-stimulating complexes (iscom) containing meningococcal PorA protein effectively generate bactericidal antibodies. Purified PorA, however, did not elicit a significant response, highlighting the importance of formulation for vaccine efficacy.
Area of Science:
- Immunology
- Vaccinology
- Microbiology
Background:
- Neisseria meningitidis poses a significant public health threat.
- The PorA outer membrane protein is a key target for meningococcal vaccines.
- Evaluating different vaccine formulations is crucial for optimizing immunogenicity.
Purpose of the Study:
- To compare the immunogenicity of various meningococcal PorA vaccine formulations.
- To assess the ability of different formulations to induce bactericidal antibodies.
- To analyze the antibody subclass responses elicited by each formulation.
Main Methods:
- Comparison of purified PorA, outer membrane vesicles (OMV), and immune-stimulating complexes (iscom) formulations.
- Assessment of antibody production, including bactericidal activity and OMV-binding antibodies.
- Analysis of IgG subclass responses (IgG1, IgG2a, IgG2b, IgG3).
Main Results:
- OMV and iscom formulations induced bactericidal antibodies, unlike purified PorA.
- Both OMV and iscom formulations showed similar immunogenicity in dose-response studies.
- PorA in OMV formulation induced a broad IgG subclass response, while iscoms favored IgG1 and antibodies against linear peptides.
Conclusions:
- Meningococcal PorA outer membrane vesicles (OMV) and immune-stimulating complexes (iscoms) are effective vaccine formulations for generating bactericidal antibodies.
- Only iscoms and OMV formulations, not purified PorA, elicit a robust immune response, including anamnestic and bactericidal antibody production.
- Formulation is critical for the immunogenic potential of PorA-based meningococcal vaccines.
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