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Proposed standardization of Neisseria meningitidis PorA variable-region typing nomenclature
C T Sacchi1, A P Lemos, M E Brandt
1Division of Medical Biology, Bacteriology Department, Adolfo Lutz Institute, São Paulo, Brazil. cls9@cdc.gov
Abstract:
Neisseria meningitidis isolates are conventionally classified by serosubtyping, which characterizes the reactivities of the PorA outer membrane protein variable-region (VR) epitopes with monoclonal antibodies (MAbs). A newer method (PorA VR typing) uses predicted amino acid sequences derived from DNA sequence analysis. The resulting classification schemes are not standardized, offering conflicting and sometimes irreconcilable data from the two methods. In this paper, we propose a standardization of the PorA VR typing nomenclature that incorporates serologic information from traditional PorA serosubtyping with molecular data from predicted VR sequences. We performed a comprehensive literature and database search, generating a collection of strains and DNA sequences that reflects the diversity within PorA that exists to date. We have arranged this information in a comprehensive logical model that includes both serosubtype and PorA VR type assignments. Our data demonstrate that the current panel of serosubtype-defining MAbs underestimates PorA VR variability by at least 50%. Our proposal for VR typing is informative because amino acid sequence and serologic information, when serosubtype-defining MAbs are available, can be deduced simultaneously from the PorA VR designation. This scheme will be useful in future classification and applied epidemiologic studies of N. meningitidis, being a systematic way of selecting PorA vaccine candidates and analyzing vaccine coverage and failure.
Insights
This study proposes a standardized nomenclature for Neisseria meningitidis PorA typing, integrating traditional serosubtyping with molecular data. This unified approach enhances classification accuracy for PorA variable regions, crucial for vaccine development and epidemiological studies.
Area of Science:
- Microbiology
- Immunology
- Genetics
Background:
- Neisseria meningitidis classification traditionally relies on PorA serosubtyping using monoclonal antibodies (MAbs).
- Emerging PorA VR typing uses DNA sequencing to predict amino acid sequences, but lacks standardization with serosubtyping.
- Discrepancies between these methods hinder accurate classification and epidemiological analysis.
Purpose of the Study:
- To propose a standardized nomenclature for PorA VR typing of Neisseria meningitidis.
- To integrate serologic data from traditional serosubtyping with molecular data from predicted PorA VR sequences.
- To provide a unified classification system for improved N. meningitidis studies.
Main Methods:
- Comprehensive literature and database search for N. meningitidis strains and PorA DNA sequences.
- Development of a logical model incorporating both serosubtype and PorA VR type assignments.
- Analysis of PorA VR variability in relation to existing serosubtype-defining MAbs.
Main Results:
- The current panel of serosubtype-defining MAbs underestimates PorA VR variability by at least 50%.
- The proposed nomenclature allows simultaneous deduction of amino acid sequence and serologic information.
- A comprehensive collection of strains and DNA sequences reflecting PorA diversity was generated.
Conclusions:
- The proposed standardized PorA VR typing nomenclature reconciles serologic and molecular data.
- This unified scheme improves the classification of N. meningitidis isolates.
- The nomenclature will aid in selecting PorA vaccine candidates and analyzing vaccine effectiveness and failure in epidemiological studies.