Fluctuations in serogroup B meningococcal vaccine antigens prior to routine MenB vaccination in France.

Background: Invasive meningococcal disease (IMD) of serogroup B is preventable by protein-based vaccines targeting one (Bivalent rLP2086 vaccine) or several variable proteins (4CMenB vaccine) at the bacterial surface. The 4CMenB was licensed in Europe in 2013 but has been recommended and reimbursed in France for infants over 2 months old since April 2022. The bivalent rLP2086 vaccine was licensed in Europe in 2017 for subjects of 10 years and older. Evaluating strain coverage and fluctuations prior to large scale vaccine use is highly informative.

Methods: We analysed invasive isolates at the French National Reference Centre for meningococci between 1975 and 2022. The 1691 recovered isolates were sequenced. We scored sex, and age groups of subjects. We also scored clonal complexes (CC) and the predicted coverage rates of the corresponding isolates using the genetic Meningococcal Antigen Typing System (gMATS) and the Meningococcal Deduced Vaccine Antigen Reactivity (MenDeVAR).

Results: The period was divided into four periods 1975-1986, 1987-1998-1999-2010 and 2011-2022. Our data clearly show significant differences in the distribution of alleles encoding the vaccine-covered antigens between these four periods. The clonal complex (CC) distribution also differed between the two periods with the disappearance of CC8 since 2011 and drastic decreases in CC11 since 1999. MenDeVar-predicted coverage fluctuated between 46.8% and 60.6% during the four periods for the 4CMenB and between 63.4% and 81.3% for rLP2086. For 4CMenB, coverage was higher using gMATS and varied between 74.5% and 85.0%. Fluctuations were also observed for all age groups.

Conclusions: IMD epidemiology is continuously changing with fluctuation in vaccine strain coverage over the 48 years prior to the routine implementation of the vaccines.