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. 2023 Aug 1;6(8):e2329678.
doi: 10.1001/jamanetworkopen.2023.29678.

Four-Component Recombinant Protein-Based Vaccine Effectiveness Against Serogroup B Meningococcal Disease in Italy

Lorenzo Lodi  1   2 , Federica Barbati  1   2 , Daniela Amicizia  3 , Vincenzo Baldo  4 , Anna Maria Barbui  5 , Alessandro Bondi  5 , Claudio Costantino  6 , Liviana Da Dalt  7 , Lorenza Ferrara  8 , Francesca Fortunato  9 , Valentina Guarnieri  1   2 , Giancarlo Icardi  3 , Giuseppe Indolfi  10   11 , Domenico Martinelli  9 , Marco Martini  12 , Maria Moriondo  13 , Francesco Nieddu  13 , Diego G Peroni  14 , Rosa Prato  9 , Silvia Ricci  1   2 , Francesca Russo  15 , Francesca Tirelli  7 , Francesco Vitale  6 , Shamez N Ladhani  16   17 , Chiara Azzari  1   2 ; Multiregional MenB study group
Collaborators, Affiliations

Four-Component Recombinant Protein-Based Vaccine Effectiveness Against Serogroup B Meningococcal Disease in Italy

Lorenzo Lodi et al. JAMA Netw Open. .

Abstract

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.

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Conflict of interest statement

Conflict of Interest Disclosures: Dr Baldo reported receiving grants from Pfizer and personal fees from Seqirus, Janssen, MSD, Moderna, and GSK outside the submitted work. Dr Icardi reported scientific support from the Department of Health Sciences (DiSSal), University of Genoa, Genoa, Italy Clinical trial during the conduct of the study. Dr Prato reported receiving personal fees from Novartis. Dr Ricci reported receiving grants from Pfizer and MSD and personal fees from Sanofi, Takeda, and Behring outside the submitted work. Dr Azzari reported receiving conference participation for Behring, Takeda, Kedrion, Sanofi, and Pfizer and personal fees from Novavax, GSK, MSD, and Eurospital outside the submitted work. No other disclosures were reported.

Figures

Figure 1.
Figure 1.. Flowchart of Eligible Individuals in the Matched Case-Control Study by Vaccination Status
Analysis 1 includes all children regardless of their age; analysis 2, only children who were old enough to receive at least the first dose of the vaccine; and analysis 3, only children old enough to be fully vaccinated after exclusion of partially immunized children.
Figure 2.
Figure 2.. Crude Incidences in the Prevaccine Era and Age-Standardized Incidence Rates in the Postvaccine Era
Error bars indicate 95% CIs.
Figure 3.
Figure 3.. Association of Type B Invasive Meningococcal Disease With Vaccination in the Matched Case-Control Study
OR indicates odds ratio.
See this image and copyright information in PMC

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