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Inducing Meningococcal Meningitis Serogroup C in Mice via Intracisternal Delivery
Published on: November 5, 2019
Genetic and immunologic characterization of a novel serotype 4, 15 strain of Neisseria meningitidis
M C Bash1, F Lynn, N F Concepcion
1Division of Bacterial Products, Center for Biologics Evaluation and Research, Food and Drug Administration, Bethesda, MD 20892, USA. bash@cber.fda.gov
Abstract:
The porin proteins of Neisseria meningitidis are important components of outer membrane protein (OMP) vaccines. The class 3 porin gene, porB, of a novel serogroup B, serotype 4, 15 isolate from Chile (Ch501) was found to be VR1-4, VR2-15, VR3-15 and VR4-15 by porB variable region (VR) typing. Rabbit immunization studies using outer membrane vesicles revealed immunodominance of individual PorB (class 3) VR epitopes. The predominant anti-Ch501 PorB response was directed to the VR1 epitope. Anti-PorB VR1 mediated killing was suggested by the bactericidal activity of Ch501 anti-sera against a type 4 strain not expressing PorA or class 5 OMPs. Studies that examine the molecular epidemiology of individual porB VRs, and the immune responses to PorB epitopes, may contribute to the development of broadly protective group B meningococcal vaccines.
Insights
Outer membrane proteins (OMPs) like porin are key for Neisseria meningitidis vaccines. This study identified specific porin variable regions (VRs) and found the VR1 epitope is a promising target for developing broadly protective vaccines.
Area of Science:
- Microbiology
- Vaccinology
- Immunology
Background:
- Porin proteins are crucial components of outer membrane protein (OMP) vaccines against Neisseria meningitidis.
- Understanding the diversity of porin proteins is essential for developing effective vaccines.
Purpose of the Study:
- To characterize the porB variable regions (VRs) of a novel Neisseria meningitidis serogroup B isolate (Ch501).
- To investigate the immunogenicity and immune response to specific porin epitopes.
- To assess the potential of porin epitopes in developing broadly protective group B meningococcal vaccines.
Main Methods:
- PorB variable region (VR) typing was performed on the Ch501 isolate.
- Rabbit immunization studies using outer membrane vesicles were conducted.
- Bactericidal activity assays were used to evaluate serum-mediated killing.
Main Results:
- The porB gene of the Ch501 isolate exhibited specific variable region types (VR1-4, VR2-15, VR3-15, VR4-15).
- Immunization studies revealed immunodominance of individual class 3 PorB VR epitopes.
- The predominant immune response was directed towards the VR1 epitope, which mediated bactericidal activity.
Conclusions:
- The VR1 epitope of class 3 porin shows potential as a target for broadly protective Neisseria meningitidis vaccines.
- Further studies on the molecular epidemiology of porB VRs and immune responses are warranted.
- Targeting specific porin epitopes may enhance the efficacy of OMP vaccines.
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