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Published on: November 5, 2019
Distribution of surface protein variants among hyperinvasive meningococci: implications for vaccine design
Rachel Urwin1, Joanne E Russell, Emily A L Thompson
1Department of Zoology, University of Oxford, Oxford, United Kingdom. rachel.urwin@zoo.ox.ac.uk
Abstract:
The bacterium Neisseria meningitidis is a major cause of meningitis and septicemia worldwide. Outer membrane proteins (OMPs) are candidates in the search for comprehensive meningococcal vaccines; however, the formulation of OMP vaccines is complicated by antigenic diversity, which is generated by high levels of genetic reassortment and strong positive selection in the meningococcal antigen genes. The genetic and antigenic diversity of three OMPs (FetA, PorA, and PorB) among a global collection of meningococcal isolates representative of the major hyperinvasive clonal complexes was determined. There was evidence for antigenic structuring among the three OMPs that could not be explained purely by descent. These observations violated the predictions of the clonal and epidemic clonal models of population structure but were in concordance with models of strain structure which propose that host immunity selects for nonoverlapping antigen combinations. The patterns of antigenic variant combinations suggested that an OMP-based vaccine with as few as six PorA and five FetA variant sequences could generate homologous immune responses against all 78 isolates examined.
Insights
Neisseria meningitidis outer membrane proteins (OMPs) show significant antigenic diversity, complicating vaccine development. A targeted vaccine using specific FetA and PorA variants could provide broad protection against meningitis and septicemia.
Area of Science:
- Microbiology
- Immunology
- Vaccine Development
Background:
- Neisseria meningitidis is a primary cause of meningitis and septicemia globally.
- Outer membrane proteins (OMPs) are key targets for meningococcal vaccines.
- Antigenic diversity in OMPs poses challenges for vaccine formulation due to genetic reassortment and selection.
Purpose of the Study:
- To determine the genetic and antigenic diversity of three OMPs (FetA, PorA, PorB) in global Neisseria meningitidis isolates.
- To investigate population structure models explaining OMP diversity.
- To assess the potential for a broadly protective OMP-based vaccine.
Main Methods:
- Analysis of genetic and antigenic variation in FetA, PorA, and PorB across diverse meningococcal isolates.
- Comparison of observed diversity patterns with clonal and strain structure models.
- Modeling of vaccine component requirements for broad coverage.
Main Results:
- Evidence of antigenic structuring in FetA, PorA, and PorB not solely explained by genetic descent.
- Observed patterns align with models where host immunity selects for nonoverlapping antigen combinations.
- A vaccine with six PorA and five FetA variants could potentially cover all 78 examined isolates.
Conclusions:
- Host immunity plays a significant role in shaping meningococcal OMP antigen combinations.
- A focused OMP-based vaccine strategy targeting specific variants is feasible.
- This approach could lead to a more effective vaccine against Neisseria meningitidis.
