Four-Component Recombinant Protein–Based Vaccine Effectiveness Against Serogroup B Meningococcal Disease in Italy
Authors: Lodi Lorenzo , Barbati Federica , Amicizia Daniela , Baldo Vincenzo , Barbui Anna Maria , Bondi Alessandro , Costantino Claudio , Da Dalt Liviana , Ferrara Lorenza , Fortunato Francesca , Guarnieri Valentina , Icardi Giancarlo , Indolfi Giuseppe , Martinelli Domenico , Martini Marco , Moriondo Maria , Nieddu Francesco , Peroni Diego G. , Prato Rosa , Ricci Silvia , Russo Francesca , Tirelli Francesca , Vitale Francesco , Ladhani Shamez N. , Azzari Chiara ,   Multiregional MenB study group, Palermo Mario , Bosco Girolama , Milisenna Rosanna , Cuccia Mario , Belbruno Franco , Castellani Giulia Tarabini , D’Angelo Claudio , Ferrera Giuseppe , Contrino Lia , Canzoneri Gaspare , Mongelli Onofrio , Albano Nehludoff , Lagravinese Domenico , Matera Riccardo , Termite Stefano , Iannucci Giovanni , Fedele Alberto , Conversano Michele , Amoruso Irene , Baldovin Tatjana , Cocchio Silvia , Bonaccorso Nicole , Sciortino Martina , Conforto Arianna , Masiero Susanna , Lombardi Daniela , Di Maggio Elisa , Meola Martina , Boscia Silvia , Tonon Michele , Masini Marzio , Piazza Maria Francesca , Sticchi Camilla 
Published: August 2023

Importance

Population-based data on the 4-component recombinant protein–based (4CMenB) vaccine effectiveness and reduction in incidence rate ratios (IRRs) are continuously needed to assess vaccine performance in the prevention of serogroup B invasive meningococcal disease (IMD).

Objective

To assess the effectiveness and reduction in IRRs associated with the 4CMenB vaccine in the pediatric population in 6 regions in Italy.

Design, Setting, and Participants

This retrospective cohort screening study and case-control study included data from children aged younger than 6 years in 6 highly populated Italian regions from January 1, 2006, to January 1, 2020. Participants included children younger than 6 years diagnosed with serogroup B IMD without predisposing factors. Data were collected from regional surveillance and vaccination registries and were analyzed from September 2021 to January 2022.

Exposures

Routine 4CMenB vaccination, per regional vaccination programs.

Main Outcomes and Measures

The main outcome was the effectiveness of the 4CMenB vaccine in the prevention of serogroup B IMD in the population of children aged younger than 6 years in 6 Italian regions. The percentages of vaccine effectiveness (VE) were obtained through the concomitant use of a screening method and a case-control study. Secondary outcomes were the comparison of effectiveness results obtained using the 2 different computational methods, the description of serogroup B IMD incidence rates, and reduction in IRRs before and after 4CMenB introduction, as a proxy for vaccine impact.

Results

The cohort screening study included a resident population of 587 561 children younger than 6 years in 3 regions with similar surveillance protocols, and the matched-case controls study assessed a resident population of 1 080 620 children younger than 6 years in 6 regions. Analyses found that 4CMenB VE in fully immunized children was 94.9% (95% CI, 83.1%-98.4%) using the screening method and 91.7% (95% CI, 24.4%-98.6%) using the case-control method. Overall reduction in IRR was 50%, reaching 70% in regions with early-start vaccination schedules. The case-control method involving 6 highly-populated Italian regions included 26 cases and 52 controls and found an estimated VE of 92.4% (95% CI, 67.6%-97.9%) in children old enough for the first vaccine dose and 95.6% (95% CI, 71.7%-99.1%) in fully immunized children. VE was more than 90% for partially immunized children. Even in regions where the first dose was administered at age 2 months, almost 20% of unvaccinated cases were among infants too young to receive the first 4CMenB dose.

Conclusions and Relevance

This screening cohort study and matched case-controls study found high effectiveness of 4CMenB vaccination and greater reduction in IRR for early-start vaccination schedules in preventing invasive serogroup B meningococcal disease. The high proportion of children too young to be vaccinated among unvaccinated cases suggests that starting the vaccination even earlier may prevent more cases. Screening and case-control methods provided similar estimates of VE: either method may be used in different study settings, but concomitant use can provide more robust estimates.