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

Abstract

ImportancePopulation-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).ObjectiveTo assess the effectiveness and reduction in IRRs associated with the 4CMenB vaccine in the pediatric population in 6 regions in Italy.Design, Setting, and ParticipantsThis 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.ExposuresRoutine 4CMenB vaccination, per regional vaccination programs.Main Outcomes and MeasuresThe 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.ResultsThe 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 RelevanceThis 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.

Insights and expectations of healthcare professionals on the implementation of the updated pediatric regional immunization Calendar in Calabria, Italy

“… 19 A recent retrospective cohort screening study, carried out in Italy, reported that earlier vaccination with the four-component MenB vaccine (4CMenB) may lead to greater protection against meningococcal infection. 9 Pellegrino et al 20 also reported that co-administration of DTaP-IPV-HB-Hib, PCV, and MenC vaccines has led to increased vaccine coverage in the LHU of Cuneo-1, from 47% to 65%, in only one year of implementation. According to evidence from experience in the United Kingdom, co-administration of such vaccines does not affect vaccine efficacy.…”

“…Adherence to the updated co-administration strategy outlined in the CIC could provide many advantages, such as fewer vaccination appointments during the first year of life, completion of the primary vaccination cycle in two sessions (compared with the standard of four), and thereby earlier vaccination, which may provide greater protection against some diseases. 8 , 9 Similar vaccination strategies have also been used previously in the United Kingdom and Portugal. 10 , 11 In the United Kingdom, vaccine co-administration led to no reductions in vaccine coverage or efficacy, and no negative impact on the overall tolerability of the vaccines.…”

4CMenB journey to the 10-year anniversary and beyond

“… 74 More recently, 4CMenB vaccine effectiveness against MenB disease in fully immunized children in three Italian regions (Tuscany, Veneto, and Piedmont) was found to be 94.9% (95% CI: 83.1–98.4) by a screening method and 91.7% (24.4–98.6) in six regions (Tuscany, Veneto, Piedmont, Apulia, Liguria, and Sicily) by a case-control method. 75 Almost 20% of the cases in unvaccinated children were among infants too young to be vaccinated, suggesting earlier vaccination may prevent more MenB disease cases.…”