Exploring the population-level impact of MenB vaccination via modeling: Potential for serogroup replacement

Abstract

Various meningococcal conjugate vaccines exist against serogroups A, C, W and Y. A new protein-based vaccine targeting serogroup B (MenB) is also now available. The potential of such vaccines to drive serogroup replacement is considered a possible public health concern when implementing nationwide routine immunization programmes. The aim of this work was to investigate if and how serogroup replacement may occur following widespread vaccination with a MenB vaccine that may protect against carriage. To that end, we built a dynamic transmission model with age and serogroup stratification, focusing on European settings where most invasive meningococcal disease (IMD) cases are caused by serogroups B and C. For illustration purposes, the model was employed in 2 such settings: UK (England and Wales) and Czech Republic. Preliminary model-based projections suggest that, under strong serogroup competition for colonization, vaccine-induced serogroup replacement may occur even with a relatively low vaccine efficacy against serogroup B carriage (e.g., 20%), with potential subsequent increase in serogroup C IMD. The magnitude and speed of the model-projected serogroup C IMD increase depend on the MenB vaccination strategy, vaccine efficacy against carriage and the extent of any potential cross-protection against other serogroups. These analyses are neither exhaustive nor definitive, and focused on simulating potential population-level trends in IMD post-vaccination, under certain assumptions. Due to present inherent limitations and uncertainties, this study has limited quantitative value and is best regarded as an explorative qualitative modeling approach, to complement and challenge the current status quo, and suggest areas where collecting additional data may be essential.

Keywords: dynamic transmission model; invasive meningococcal disease; mathematical modeling; serogroup B meningococcal vaccine; serogroup replacement.

Figure 1.

(A) Illustration of best model fit against the synthesized carriage prevalence data at baseline, age-and serogroup-stratified, for the UK setting. (B) Illustration of best model fits against the IMD data for the UK setting (England and Wales) at baseline: annual number of cases, age-and serogroup-stratified. Left panel, "High-incidence IMD scenario," based on IMD data in 1998/1999; right panel, "Low-incidence IMD scenario" based on averaged IMD data from 2005–2009. Data-points corresponding to the following age groups (in years):<1, 1–4, 5–9, 10–14, 15–19, 20–24 and ≥25 .

Figure 2.

Model-projected potential trends in the annual number of IMD cases over time in the UK setting (England and Wales) following routine MenB infant vaccination with routine booster at 1 y of age starting from an unaltered high-incidence IMD scenario at baseline (scenario 1). Serogroup-specific IMD (pooled across all age groups) and total IMD across all serogroups. (A) 20% assumed vaccine efficacy against serogroup B carriage. (B) 60% assumed vaccine efficacy against serogroup B carriage. Vaccine coverage: 85%. Vaccine efficacy against serogroup B IMD: 78%. No cross-protection effects.

Figure 3.

Model-projected potential trends in the annual number of IMD cases over time in the UK setting (England and Wales) following routine MenB infant vaccination with routine booster at 1 y of age, starting from a low-incidence IMD scenario at baseline (scenario 2). Serogroup-specific IMD (pooled across all age groups) and total IMD across all serogroups. (A) 20% assumed vaccine efficacy against serogroup B carriage. (B) 60% assumed vaccine efficacy against serogroup B carriage. Vaccine coverage: 85%. Vaccine efficacy against serogroup B IMD: 78%. No cross-protection effects.

Figure 4.

Model-projected trends in the annual number of IMD cases over time in the UK setting (England and Wales) following routine MenB infant only (no booster) vaccination plus a one-time MenB catch-up campaign in 1–17 y old, starting from an unaltered high-incidence IMD scenario at baseline (scenario 3). Serogroup-specific IMD (pooled across all age groups) and total IMD across all serogroups. (A) 20% vaccine efficacy serogroup B carriage, 78% vaccine efficacy serogroup B IMD, no cross-protection. (B) 20% and 78% vaccine efficacy serogroup B carriage and IMD, respectively, 10% and 80% cross-protective efficacy serogroup C carriage and IMD, respectively, and 5% and 50% cross-protective efficacy all Others carriage and IMD, respectively. Vaccine coverage: age-dependent.

Figure 5.

Model-projected trends in the annual number of IMD cases over time in the UK setting (England and Wales) following routine MenB infant only (no booster) vaccination plus a one-time MenB catch-up campaign in 1–17 y old, starting after 15 y of similar vaccination strategy with a MenC vaccine (scenario 4). Serogroup-specific IMD (pooled across all age groups) and total IMD across all serogroups. (A) 20% vaccine efficacy serogroup B carriage, 78% vaccine efficacy serogroup B IMD, no cross-protection. (B) 20% and 78% vaccine efficacy serogroup B carriage and IMD, respectively, with 10% and 80% cross-protective efficacy serogroup C carriage and IMD, respectively, and 5% and 50% cross-protective efficacy all Others carriage and IMD, respectively.

Figure 6.

Model-projected trends in the annual number of IMD cases over time in the UK setting (England and Wales) following routine MenB adolescent vaccination at the age of 17 y old, starting from an unaltered high-incidence IMD scenario at baseline (scenario 5). Serogroup-specific IMD (pooled across all age groups) and total IMD across all serogroups. (A) 20% assumed vaccine efficacy against serogroup B carriage, 78% vaccine efficacy against serogroup B IMD, no cross-protection. (B) 20% and 78% assumed vaccine efficacy against serogroup B carriage and IMD, respectively, 10% and 80% assumed cross-protective efficacy against serogroup C carriage and IMD, respectively, and 5% and 50% assumed cross-protective efficacy against all Others carriage and IMD, respectively. Vaccine coverage: 60%.

Figure 7.

Model-projected trends in the annual number of IMD cases over time in the UK setting (England and Wales) following routine MenB adolescent vaccination at the age of 17 y old, starting after 15 y of similar vaccination strategy with a MenC vaccine (scenario 6). Serogroup-specific IMD (pooled across all age groups) and total IMD across all serogroups. (A) 20% vaccine efficacy against serogroup B carriage, 78% vaccine efficacy against serogroup B IMD, no cross-protection. (B) 20% and 78% vaccine efficacy against serogroup B carriage and IMD, respectively, 10% and 80% cross-protective efficacy against serogroup C carriage and IMD, respectively, and 5% and 50% cross-protective efficacy against all Others carriage and IMD, respectively. Vaccine coverage: 60%.

Figure 8.

Model-projected potential trends in the annual number of IMD cases over time in the UK setting (England and Wales) following routine MenB adolescent vaccination at the age of 17 y old, starting from a low-incidence IMD scenario at baseline (scenario 7). Serogroup-specific IMD (pooled across all age groups) and total IMD across all serogroups. (A) 20% vaccine efficacy against serogroup B carriage, 78% vaccine efficacy against serogroup B IMD, no cross-protection. (B) 20% and 78% vaccine efficacy against serogroup B carriage and IMD, respectively, 10% and 80% cross-protective efficacy against serogroup C carriage and IMD, respectively, and 5% and 50% cross-protective efficacy against all Others carriage and IMD, respectively. Vaccine coverage: 60%.

Figure 9.

Illustration of best fit model for the Czech setting at baseline, with age and serogroup stratification. Left panel: model fit against the synthesized carriage prevalence data. Right panel: model fit against the IMD data (annual number of cases, with data-points corresponding to the following age groups (in years):<1, 1–4, 5–9, 10–14, 15–19, 20–24, 25–34, 35–44, 45–54, 55–64 and ≥65 ). NRL, National Reference Laboratory for Meningococcal Infections, National Institute of Public Health, Prague, Czech Republic.

Figure 10.

Model-projected potential trends in the annual number of IMD cases over time in the Czech Republic following routine MenB infant vaccination with routine booster at 1 y of age (scenario 1). Serogroup-specific IMD (pooled across all age groups) and total IMD across all serogroups shown in the top panels. (A) 20% assumed vaccine efficacy against serogroup B carriage. (B) 60% assumed vaccine efficacy against serogroup B carriage. Vaccine coverage: 85%. Vaccine efficacy against serogroup B IMD: 78%. No cross-protection effects.

Figure 11.

Model-projected potential trends in the annual number of IMD cases over time in the Czech Republic following routine MenB adolescent vaccination at the age of 17 y old (scenario 5). Serogroup-specific IMD (pooled across all age groups) and total IMD across all serogroups shown. (A) 20% assumed vaccine efficacy against serogroup B carriage, 78% vaccine efficacy against serogroup B IMD, no cross-protection. (B) 20% and 78% assumed vaccine efficacy against serogroup B carriage and IMD, respectively, 10% and 80% assumed cross-protective efficacy against serogroup C carriage and IMD, respectively, and 5% and 50% assumed cross-protective efficacy against all Others carriage and IMD, respectively. Vaccine coverage: 60%.

Figure 12.

Model-projected trends in the annual number of IMD cases over time in the Czech Republic following routine MenB adolescent vaccination at the age of 17 y old, starting after 15 y of similar vaccination strategy with a MenC vaccine (scenario 6). Serogroup-specific IMD (pooled across all age groups) and total IMD across all serogroups in the top panels. (A) 20% vaccine efficacy against serogroup B carriage, 78% vaccine efficacy against serogroup B IMD, no cross-protection. (B) 20% and 78% vaccine efficacy against serogroup B carriage and IMD, respectively, 10% and 80% cross-protective efficacy against serogroup C carriage and IMD, respectively, and 5% and 50% cross-protective efficacy against all Others carriage and IMD, respectively. Vaccine coverage: 60%.

Figure 13.

Baseline model structure with states and flows.