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Evolution of strain coverage by the multicomponent meningococcal serogroup B vaccine (4CMenB) in France
Eva Hong1, Aude Terrade1, Alessandro Muzzi2
1Institute Pasteur, Invasive Bacterial Infections Unit, Paris, France.
Abstract:
The 4CMenB, a protein-based vaccine, was licensed in Europe in 2013 against invasive meningococcal disease caused by serogroup B and is currently implemented in several countries although according to different national strategies. Isolate coverage estimation is required as vaccine-targeted antigens may vary among isolates over time. Several phenotypic and genotypic methods have been developed to predict strain coverage by scoring the expression and cross-reactivity of vaccine antigens using the Meningococcal Antigen Typing system (MATS), by the genetic correlation of alleles encoding these antigens and MATS expression data (gMATS) and by the Meningococcal Deduced Vaccine Antigen Reactivity (MenDeVAR). We applied these approaches on meningococcal B isolates in France and compared two epidemiological years, 2013-2014 and 2018-2019. A strong correlation was observed between MATS data that were generated for the year 2013-2014 and the gMATS data extracted from whole genome sequencing. gMATS and MenDeVAR were next used to compare the two years. Using gMATS, the overall coverage was 77.2% (lower limit (LL)-upper limit (UL) 66.7-87.7) and 70.7% (LL-UL 61.5-80.0) for the two years, respectively. The reduction in coverage between the two years is mainly driven by the reduction of alleles exactly matching the vaccine antigens. A high number of unpredictable isolates was observed using the MenDeVAR and was due to lack of MATS information for new or rare alleles in particular for the year 2018-2019. Our data underline the need of continuous surveillance of strain coverage and the importance of generating phenotypic MATS data to update the genetic approaches of prediction.
Insights
The 4CMenB vaccine
Area of Science:
- Microbiology
- Vaccinology
- Epidemiology
Background:
- The 4CMenB vaccine, licensed in 2013, targets invasive meningococcal disease caused by serogroup B.
- Estimating vaccine strain coverage is crucial due to potential variations in vaccine-targeted antigens over time.
- Phenotypic and genotypic methods like MATS, gMATS, and MenDeVAR have been developed for coverage prediction.
Purpose of the Study:
- To apply and compare phenotypic and genotypic methods for estimating 4CMenB vaccine coverage in French Neisseria meningitidis serogroup B isolates.
- To assess changes in vaccine strain coverage between the 2013-2014 and 2018-2019 epidemiological years.
Main Methods:
- Utilized the Meningococcal Antigen Typing system (MATS) for phenotypic antigen expression and cross-reactivity.
- Employed genetic MATS (gMATS) correlating whole genome sequencing data with MATS expression.
- Applied Meningococcal Deduced Vaccine Antigen Reactivity (MenDeVAR) for prediction, comparing two epidemiological periods in France.
Main Results:
- A strong correlation was found between MATS and gMATS data from 2013-2014.
- Overall coverage estimated by gMATS decreased from 77.2% (2013-2014) to 70.7% (2018-2019).
- The decrease in coverage was primarily due to fewer isolates with alleles exactly matching vaccine antigens; MenDeVAR identified many unpredictable isolates, especially in 2018-2019.
Conclusions:
- Continuous surveillance of meningococcal B strain coverage is essential for effective vaccine strategies.
- Phenotypic MATS data generation is vital for updating and validating genetic prediction methods like gMATS and MenDeVAR.
- The observed reduction in coverage highlights the dynamic nature of meningococcal populations and the need for ongoing monitoring.

