Public Health Impact and Cost-Effectiveness of Revising the Adolescent Meningococcal Vaccine Schedule in the United States

Abstract

Background

In 2025, invasive meningococcal disease (IMD) vaccination in United States (US) adolescents consisted of two standard of care (SoC) schedules: Q-Q-B-B (routine MenACWY [Q] at ages 11 and 16 years; MenB [B] under shared clinical decision-making [SCDM] at age 16 years and 6 months later) or Q-P-B (routine MenACWY at ages 11 and 16 years; MenABCWY [P] at age 16 years and MenB under SCDM 6 months later). We assessed public health impact (PHI) and cost-effectiveness (CE) of intervention strategies on the basis of potential implementation options and revisions to the adolescent meningococcal vaccine schedule proposed in June 2024 by the Centers for Disease Control and Prevention’s Advisory Committee on Immunization Practices.

Methods

A model utilizing epidemiological and economic inputs compared projected outcomes for 27 intervention strategies (distinguished by vaccine type [Q, P, and/or B], recommendation type [routine, risk-based], and dosing interval for MenB-containing vaccines [0,6-month , 0,24-month]) versus no vaccination or SoC over 15 years (2025–2039). Discounted outcomes (societal perspective) included IMD cases, deaths, and quality-adjusted life-year losses averted; total direct and indirect costs; and incremental CE ratios.

Results

Retaining routine MenACWY at age 11−12 years and including routine or risk-based MenB-containing vaccines at age 16 years improved PHI versus SoC, particularly with 0,6-month dosing interval for MenB-containing vaccines. Five strategies incorporating MenABCWY improved PHI and were cost-saving versus SoC: Q-Q-B-B.

Conclusions

Adolescent meningococcal vaccine schedule revisions retaining routine MenACWY and incorporating risk-based or routine MenABCWY may increase PHI in a cost-effective manner, minimizing the humanistic and economic burden of IMD.

Graphical Abstract

Supplementary Information

The online version contains supplementary material available at 10.1007/s40273-026-01599-z.

Key Points

Invasive meningococcal disease (IMD) is an uncommon but serious illness caused by the bacterium Neisseria meningitidis, associated with five common serogroups in the US (A, B, C, W, and Y). Despite the severity of IMD and existing Centers for Disease Control and Prevention (CDC) vaccine recommendations, many eligible individuals remain unvaccinated, particularly against serogroup B (MenB).

This model assessed the public health impact (PHI) and cost-effectiveness of 27 vaccine intervention strategies versus no vaccination (NV) and the two 2025 standard of care (SoC) strategies.

Five strategies that both retained routine quadrivalent (MenACWY; Q) vaccination at age 11–12 years and incorporated the pentavalent (MenABCWY; P) vaccine improved PHI and resulted in cost savings relative to an SoC strategy that did not incorporate MenABCWY.

Retaining routine MenACWY and incorporating the MenABCWY vaccine into the adolescent meningococcal vaccination schedule may improve public health while fully offsetting costs, presenting an opportunity to reduce the burden of this devastating disease.

Introduction

Although uncommon, invasive meningococcal disease (IMD), caused by the bacterium Neisseria (N.) meningitidis, is a serious illness with a substantial humanistic and economic burden, characterized by sudden onset, rapid progression, serious clinical presentation, and high case-fatality rates [1]. Up to 40% of individuals who survive acute IMD infection experience long-term physical and neurological sequelae including hearing and vision impairments, amputations, and psychiatric conditions such as anxiety and depression, which can have a lasting emotional, social, and financial impact on both patients and their caregivers [2–9]. In the United States (US), the highest incidence of IMD is among infants and children, with another peak in incidence reported among adolescents and young adults aged 16–23 years. N. meningitidis serogroups A, B, C, W, and Y are responsible for the majority of US IMD cases, with serogroup B accounting for most cases of IMD in adolescents [10, 11].

In the US, vaccines are available to protect against the five most common serogroups associated with IMD: quadrivalent MenACWY vaccines (serogroups A, C, W, and Y [Q]); monovalent MenB vaccines (serogroup B [B]); and pentavalent MenABCWY vaccines (serogroups A, B, C, W, and Y [P]) [12, 13]. For adolescents, the Centers for Disease Control and Prevention (CDC) and other recommending bodies recommend initiation of the MenACWY vaccination series for those aged 11–12 years, with a booster at age 16 years [14]; on 5 January 2026, the US Department of Health and Human Services announced that the MenACWY doses at ages 11–12 years and 16 years were changed from a routine CDC recommendation to shared clinical decision-making (SCDM) [15, 16]. The CDC recommends MenB vaccination under SCDM for individuals aged 16–23 years (preferably for those aged 16–18 years) [14]. In 2023, the CDC provided an additional recommendation that a MenABCWY vaccine [Penbraya, Pfizer] may be administered when both MenACWY and MenB are indicated in the same visit [13, 17]. In July 2025, the CDC’s Advisory Committee on Immunization Practices (ACIP) extended this recommendation to include another approved MenABCWY vaccine [Penmenvy, GSK] [18]. For individuals considered to be at high risk of IMD, the CDC recommends routine MenACWY vaccination for those aged ≥ 2 months and routine MenB vaccination for those aged ≥ 10 years [12, 14].

Despite the availability of effective vaccines in the US, substantial opportunities exist for improved IMD prevention. For example, coverage of the MenACWY vaccine is lower in older adolescents than in younger adolescents; a 2023 study found that while 88% of those aged 13–17 years had received an initial dose of MenACWY, only 60% had received the MenACWY booster dose by age 17 years [19, 20]. Furthermore, uptake rates of both one and two doses of the MenB vaccine by age 17 years were substantially lower than those of the MenACWY vaccine, at only 32% and 13%, respectively, in 2023 [19, 20]. There are currently no data available regarding uptake of or coverage with the MenABCWY vaccine.

Several barriers limit the uptake of available IMD vaccines; previous studies have indicated a lack of knowledge and awareness regarding IMD and meningococcal vaccine recommendations among healthcare professionals (HCPs), patients, and parents. In a 2022 study, 61% of patients aged 16–23 years displayed shortcomings in their knowledge of IMD and 52% had a limited understanding of why both the MenACWY and MenB vaccines were needed to maximize protection [21]. A similar study from 2020 found that 57% of parents were unaware of the existence of the MenB vaccine, with 36% of these individuals reporting interest in seeking relevant information from their HCP [22]. HCPs have expressed a need for additional time to educate patients on IMD when recommending MenB vaccination under SCDM, and have noted that the SCDM recommendation can result in confusion among both HCPs and patients and/or parents, suggesting that limited and inconsistent coverage across vaccines may be a result of varying recommendation types [21, 23]. Furthermore, multiple studies have demonstrated that healthcare visits are less frequent among older versus younger adolescents, potentially limiting vaccination opportunities as patients age [24–27].

In June 2024, the ACIP discussed five options for a revised adolescent meningococcal vaccine schedule, which vary in vaccines administered, vaccine recommendation types, age at vaccination, and dosing intervals for MenB-containing vaccines (i.e., MenB or MenABCWY vaccines) [12]. Each variation is likely to impact the real-world implementation of the meningococcal vaccine schedule in the US, subsequently affecting vaccine coverage and levels of protection against IMD.

Previous analyses have evaluated the public health impact (PHI) and cost-effectiveness (CE) of a variety of vaccine strategies within proposed schedule revisions [28, 29]; however, no study has evaluated the potential PHI and CE of all schedule revision options under consideration by the ACIP. To further elucidate the impact of potential meningococcal vaccine schedule revisions, a health economic model was developed to estimate both the PHI and CE of different intervention strategies within the proposed ACIP schedule options and determine strategies that improve PHI in a cost-effective manner compared with standard of care (SoC) strategies as of 2025.

Methods

A model previously described by Shah et al. was used to estimate and compare the PHI and CE of implementing a US meningococcal immunization intervention strategy versus a comparator strategy in adolescents [28].

Schedule Options

In 2025, recommendations for vaccines to protect against IMD caused by serogroups A, B, C, W, and Y in US adolescents consisted of two schedules: (1) routine quadrivalent MenACWY (Q) at ages 11 and 16 years, monovalent MenB (B) under SCDM at ages 16–23 years, and B 6 months later (Q-Q-B-B); or (2) routine Q at ages 11 and 16 years, pentavalent MenABCWY (P) under SCDM at age 16–23 years, and B 6 months later (Q-P-B). These were considered standard of care in the model as they represented the CDC recommendations at the time of the study [12, 13].

The ACIP proposed five alternative meningococcal vaccine schedule options in June 2024, defined in terms of the number of serogroup-protecting vaccine doses to be administered, and reflecting differential vaccine recommendation types (i.e., routine, risk-based), ages at vaccine administration, and dose intervals for MenB-containing vaccine series (Table 1) [12].

Table 1.

Adolescent meningococcal vaccine schedule options proposed by the ACIP in June 2024

Schedule	Vaccines given at this age
	11 years, 0 months	15 years, 0 months	16 years, 0 months	16 years, 6 months	18 years, 0 months	18 years, 6 months
Option 1: Q-Q-B-B	Qroutine	–	Qroutine Broutine	–	Broutine	–
Option 2: Q-Q-B-B	Qroutine	–	Qroutine Brisk-based	–	Brisk-based	–
Option 3: N-Q-B-B	–	–	Qroutine Brisk-based	–	Brisk-based	–
Option 4: Q-Q-B-B	–	Qroutine	–	–	Qroutine Broutine	Broutine
Option 5: N-Q-B-B	–	–	Qroutine Broutine	–	Broutine	–

Schedule options 1–5 discussed at the June 2024 ACIP meeting. Routine refers to routine vaccine recommendation. Risk-based refers to vaccine recommendation for only those who are at high risk of contracting IMD (e.g., college students). SCDM refers to vaccine recommendation under SCDM

ACIP, Advisory Committee on Immunization Practices; B, MenB vaccine; Men, meningococcal; N, no vaccine given; Q, MenACWY vaccine; SCDM, shared clinical decision-making

The five schedule options proposed by the ACIP informed the 27 unique vaccination strategies evaluated within the model (Table 2). Within each schedule option, multiple strategies were considered, varying on the basis of the type of vaccine (e.g., use of P in place of Q and B), type of recommendation (routine, risk-based), and dosing interval for MenB-containing vaccines (0,24-month, 0,6-month). Relative to SoC, the schedule options proposed by the ACIP (and their corresponding strategies) incorporate higher population-level coverage for MenB-containing vaccines due to routine recommendations (schedule options 1, 4, and 5) or risk-based recommendations (schedule options 2 and 3) for MenB-containing vaccines. Vaccine strategies were also distinguished on the basis of expected coverage for each vaccine dose, which would, in turn, affect public health impact. The 0,24-month dose interval (all a–c scenarios) was included to capture the ACIP’s consideration that longer dose intervals may provide extended protection against MenB at older ages. Populations at a higher risk of IMD due to serogroup B (i.e., healthy adolescents eligible for a risk-based recommendation) were defined as adolescents planning to attend college or those in congregate living situations (e.g., foster care, boarding school, correctional facilities). These designations were based on proposed CDC/ACIP definitions [30]. Intervention strategies with a 0,6-month dose interval were evaluated in alignment with Food and Drug Administration (FDA) labeling and potential improved implementation feasibility with a shorter dose interval due to more frequent HCP visits and higher MenB coverage rates at younger ages [21, 31–35].

Table 2.

Intervention strategies derived from the meningococcal vaccine schedule options proposed by the ACIP and evaluated in the model

Strategy	Vaccines given at this age
	11 years, 0 months	15 years, 0 months	16 years, 0 months	16 years, 6 months	18 years, 0 months	18 years, 6 months
Comparator strategies: NV and 2025 SoCa
NV	–	–	–	–	–	–
SoC: Q-Q-B-B (coverage)b	Qroutine (88.4%)	–	Qroutine (59.7%) BSCDM (32.4%)	BSCDM (12.8%)	–	–
SoC: Q-P-B (coverage)b	Qroutine (88.4%)	–	Qroutine (27.3%) PSCDM (32.4%)	BSCDM (12.8%)	–	–
0,24-month dose interval for MenB-containing vaccinesc
Intervention strategies for schedule option 1: Q-Q-B-B, Qroutine at ages 11 and 16 years, Broutine at age 16 years and 18 years
Q-Q-B-B (1a) (coverage)b	Qroutine (88.4%)	–	Qroutine (59.7%) Broutine (59.7%)	–	Broutine (20.9%)	–
Q-P-P (1b) (coverage)b	Qroutine (88.4%)	–	Proutine (59.7%)	–	Proutine (20.9%)	–
Q-P-B (1c) (coverage)b	Qroutine (88.4%)	–	Proutine (59.7%)	–	Broutine (20.9%)	–
Intervention strategies for schedule option 2: Q-Q-B-B, Qroutine at ages 11 and 16 years, Brisk-based at age 16 years and 18 years
Q-Q-B-B (2a) (coverage)b	Qroutine (88.4%)	–	Qroutine (59.7%) Brisk-based (43.2%)	–	Brisk-based (15.1%)	–
Q-P-P (2b) (coverage)b	Qroutine (88.4%)	–	Qroutine (16.5%) Prisk-based (43.2%)	–	Prisk-based (15.1%)	–
Q-P-B (2c) (coverage)b	Qroutine (88.4%)	–	Qroutine (16.5%) Prisk-based (43.2%)	–	Brisk-based (15.1%)	–
Intervention strategies for schedule option 3: N-Q-B-B, Qroutine at age 16 years, Brisk-based at ages 16 years and 18 years
N-Q-B-B (3a) (coverage)b	–	–	Qroutine (59.7%) Brisk-based (43.2%)	–	Brisk-based (15.1%)	–
N-P-P (3b) (coverage)b	–	–	Qroutine (16.5%) Prisk-based (43.2%)	–	Prisk-based (15.1%)	–
N-P-B (3c) (coverage)b	–	–	Qroutine (16.5%) Prisk-based (43.2%)	–	Brisk-based (15.1%)	–
Intervention strategies for schedule option 5: N-Q-B-B, Qroutine at age 16 years, Broutine at ages 16 years and 18 years
N-Q-B-B (5a) (coverage)b	–	–	Qroutine (59.7%) Broutine (59.7%)	–	Broutine (20.9%)	–
N-P-P (5b) (coverage)b	–	–	Proutine (59.7%)	–	Proutine (20.9%)	–
N-P-B (5c) (coverage)b	–	–	Proutine (59.7%)	–	Broutine (20.9%)	–
0,6-month dose interval for MenB-containing vaccines
Intervention strategies for schedule option 1: Q-Q-B-B, Qroutine at ages 11 and 16 years, Broutine at ages 16 years and 16 years and 6 months
Q-Q-B-B (1d) (coverage)b	Qroutine (88.4%)	–	Qroutine (59.7%) Broutine (59.7%)	Broutine (33.2%)	–	–
Q-P-P (1e) (coverage)b	Qroutine (88.4%)	–	Proutine (59.7%)	Proutine (33.2%)	–	–
Q-P-B (1f) (coverage)b	Qroutine (88.4%)	–	Proutine (59.7%)	Broutine (33.2%)	–	–
Intervention strategies for schedule option 2: Q-Q-B-B, Qroutine at ages 11 and 16 years, Brisk-based at ages 16 years and 16 years and 6 months
Q-Q-B-B (2d) (coverage)b	Qroutine (88.4%)	–	Qroutine (59.7%) Brisk-based (43.2%)	Brisk-based (24.0%)	–	–
Q-P-P (2e) (coverage)b	Qroutine (88.4%)	–	Qroutine (16.5%) Prisk-based (43.2%)	Prisk-based (24.0%)	–	–
Q-P-B (2f) (coverage)b	Qroutine (88.4%)	–	Qroutine (16.5%) Prisk-based (43.2%)	Brisk-based (24.0%)	–	–
Intervention strategies for schedule option 3: N-Q-B-B, Qroutine at age 16 years, Brisk-based at ages 16 years and 16 years and 6 months
N-Q-B-B (3d) (coverage)b	–	–	Qroutine (59.7%) Brisk-based (43.2%)	Brisk-based (24.0%)	–	–
N-P-P (3e) (coverage)b	–	–	Qroutine (16.5%) Prisk-based (43.2%)	Prisk-based (24.0%)	–	–
N-P-B (3f) (coverage)b	–	–	Qroutine (16.5%) Prisk-based (43.2%)	Brisk-based (24.0%)	–	–
Intervention strategies for schedule option 4: Q-Q-B-B, Qroutine at ages 15 and 18 years, Broutine at ages 18 years and 18 years and 6 months
Q-Q-B-B (4d) (coverage)b	–	Qroutine (59.7%)	–	–	Qroutine (53.1%) Broutine (53.1%)	Broutine (14.9%)
Q-P-P (4e) (coverage)b	–	Qroutine (59.7%)	–	–	Proutine (53.1%)	Proutine (14.9%)
Q-P-B (4f) (coverage)b	–	Qroutine (59.7%)	–	–	Proutine (53.1%)	Broutine (14.9%)
Intervention strategies for schedule option 5: N-Q-B-B, Qroutine at age 16 years, Broutine at ages 16 years and 16 years and 6 months
N-Q-B-B (5d) (coverage)b	–	–	Qroutine (59.7%) Broutine (59.7%)	Broutine (33.2%)	–	–
N-P-P (5e) (coverage)b	–	–	Proutine (59.7%)	Proutine (33.2%)	–	–
N-P-B (5f) (coverage)b	–	–	Proutine (59.7%)	Broutine (33.2%)	–	–

Routine refers to routine vaccine recommendation. Risk-based refers to vaccine recommendation for only those who are at high risk of contracting IMD (e.g., college students). SCDM refers to vaccine recommendation under SCDM

B, MenB vaccine; IMD, invasive meningococcal disease; Men, meningococcal; N, no vaccine given; NV, no vaccination; P, MenABCWY vaccine; Q, MenACWY vaccine; SCDM, shared clinical decision-making; SoC, standard of care

^aOn 5 January 2026, the US Department of Health and Human Services announced that the MenACWY doses at ages 11–12 years and 16 years were changed from a routine recommendation to SCDM [15, 16]. However, routine recommendations for these doses were considered the standard of care in the model as they represented the recommendations at the time of the study [14]

^bSupplementary Table 7 details the sources and assumptions for vaccine coverage rates [19, 20]

^cIntervention strategies including P in schedule option 4 (Q routine at age 15 and 18 years, and B routine with two doses at age 18 years) were not included, as a 24-month dose interval for MenB-containing vaccines at age 18 years does not apply

The 27 intervention strategies were evaluated against comparator strategies, including no vaccination (NV) and SoC (Q-Q-B-B and Q-P-B; Table 2). A funnel approach was used, with PHI evaluated for all 27 intervention strategies, but CE only evaluated for strategies that improved PHI versus the SoC.

Model Structure

The model structure consisted of an epidemiological component to estimate IMD cases and an economic component to estimate the health and economic outcomes associated with IMD cases and vaccination costs incurred under the intervention and comparator strategies; a direct comparison of population-based health and economic outcomes between the intervention and comparator strategies was conducted. The model framework summarizing the CE and PHI analysis is presented in Fig. 1. The base case analysis evaluated the following outcomes of interest: IMD cases averted, IMD deaths averted, quality-adjusted life year (QALY) losses averted, incremental total societal costs, and incremental cost-effectiveness ratios (ICERs).

Fig. 1.

Model structure. This figure summarizes the model framework to assess the PHI and CE of meningococcal vaccination intervention strategies. AEs included in the model represent serious AEs. AE adverse event, CE cost-effectiveness, IMD invasive meningococcal disease, PHI public health impact

Epidemiological Component

The epidemiological component estimated the IMD cases associated with each intervention strategy by utilizing population demographics, IMD incidence, vaccine coverage, and vaccine effectiveness data. Details of the methodology for the epidemiological component have been published previously by Shah et al. [28].

In summary, compartments segmented the population by protection status against MenB and MenACWY. Further, within each status, individuals were designated as those susceptible to carriage and those who were active carriers of each of three serogroup categories (B; A, C, W, and Y; and “other” pathogenic and non-pathogenic types; Supplementary Fig. 1).

When an individual received a vaccination, they moved from a compartment without protection to one with protection against a particular serogroup. The rate of transition between the unprotected and protected compartments was a function of vaccination coverage and efficacy as well as the number of individuals already protected against a particular IMD serogroup at the time of a transmission event. Not all vaccinated individuals acquired initial vaccination protection, however, and some that did initially acquire protection lost it due to waning. Acquisition of carriage resulted in transition from a susceptible compartment to a carriage compartment; upon recovery from carriage, those individuals transitioned back to a susceptible compartment. A portion of individuals who were carriers (and not protected against the serogroup they carried) developed IMD; carriers who were protected against the serogroup they carried did not develop IMD caused by that serogroup. Although transmission of meningococcal carriage was modeled dynamically, it was assumed that meningococcal carriage would be unaffected by vaccination against IMD caused by serogroup B or serogroups A, C, W, and Y, as there is limited evidence supporting carriage protection from meningococcal vaccination in the US. Given this paucity of evidence regarding carriage protection, carriage was assumed to be unaffected by vaccination and the model behaved similar to a static population-based model, with indirect effects (i.e., herd effects) of vaccination not captured. The decision to regard the model as static in nature served to avoid introducing uncertainties stemming from unknown vaccine effects on meningococcal carriage.

Economic Component

The economic component of the model was informed by the results of the epidemiological component as well as data concerning IMD health outcomes, IMD-related costs, and costs associated with vaccination.

The likelihood of death and sequelae per IMD case was calculated, as well as health and economic outcomes associated with each case. The 16 physical, psychological, and neurological IMD sequelae (Supplementary Table 1) were selected on the basis of the conclusions of a published panel of expert clinicians [8] and informed by available literature [2, 36–38]. Due to a lack of US-specific data on co-occurrence of sequelae, the incidence of each sequela was assumed to be independent of the incidence of other sequelae. Vaccination costs incurred under the intervention and comparator strategies were calculated as a function of vaccination coverage estimates and costs for acquisition, administration, and vaccine-related serious adverse events. Productivity losses related to receiving the vaccine were not included, as it was assumed that IMD vaccination would be administered as part of an existing preventive visit, thus additional productivity losses specific to IMD vaccination would not be incurred.

The base case analysis assumed a societal perspective, accounting for all costs incurred by the healthcare system (including all vaccination costs, direct costs for acute IMD care, and any direct costs associated with medical care for long-term sequelae), as well as special education and indirect costs (productivity losses for patients and caregivers) due to acute IMD and sequelae.

Model Overview

Population

The modeled population consisted of the entire US population. Population estimates were stratified into 100 single-year age groups, between those aged 0–99 years, at the start of the model and modified on the basis of projected birth and all-cause death rates over time. Both meningococcal carriers and individuals considered to be protected against serogroups A, C, W, and Y due to vaccination prior to the start of the time horizon (2015) were included. Newborns entered the model at the beginning of each year on the basis of US birth projections, with mortality occurring at the end of each monthly model time step.

Time Horizon

A 10-year initialization period began in 2015 (2015–2024) to reflect the period when both the MenACWY and MenB vaccines were available in the US, IMD incidence was relatively stable, and vaccination was assumed to be consistent with the SoC: Q-Q-B-B strategy. Following the initialization period, a 15-year evaluation period began in 2025, when the intervention and comparator strategies were assumed to begin; outcomes for the PHI and CE analyses were collected for the IMD cases occurring during 2025–2039 (15-year timespan). This evaluation time horizon was selected in alignment with the IMD CE assessments conducted by the CDC and GSK and presented during ACIP meetings in 2023 and 2024 [29, 39, 40]. Lifetime outcomes were collected for individuals with IMD, capturing the impact of IMD through direct and indirect long-term sequelae costs for each IMD case that occurred during the 15-year time horizon. Lifetime productivity loss costs due to premature death from IMD, as well as lifetime QALYs lost due to premature death from IMD or sequelae, were collected.

Discount Rate

An annual discount rate of 3% was applied to all costs, life-years, and QALYs, including future costs and utility decrements resulting from long-term IMD sequelae (calculated on the basis of a patient’s remaining life expectancy) and costs and utilities incurred due to acute IMD (discounted on the basis of the year the IMD case occurred) [41]. The 2025 vaccine prices were used; all costs in the analysis were reported in 2025 US dollars, with cost inputs that were not originally reported in 2025 US dollars converted to that cost year using the medical care component of the US Consumer Price Index for direct medical costs and the General US Gross Domestic Product Price Deflator for indirect costs [42, 43].

Base Case Inputs

IMD incidence and case-fatality inputs were sourced from national surveillance data summarized in the CDC’s June 2023 ACIP meeting and published literature, respectively [37, 44]. Vaccine characteristics for each intervention strategy were sourced from the literature, clinical trial data, or on the basis of model assumptions. The epidemiological inputs utilized for the base case of this analysis were unchanged from those used to evaluate the PHI of IMD intervention strategy revisions, as detailed by Shah et al. [28], and are provided in Supplementary Table 1.

All cost inputs were obtained from published literature and national costing sources, including the Healthcare Cost and Utilization Project and Centers for Medicare and Medicaid Services (CMS) Physician Fee Schedule databases [45, 46]. Data regarding utilities, incidence, and costs associated with IMD sequelae were sourced from the published literature, expert clinical opinion, and/or assumptions (Supplementary Table 2).

Data on vaccine cost and coverage per intervention strategy were obtained from published literature and assumptions (Supplementary Table 3; Table 2), with MenABCWY inputs informed by the CDC’s analysis of the GSK MenABCWY vaccine [29, 47]. Vaccine prices were calculated using a weighted average of the actual public and private sector costs for each vaccine, the estimated market shares for each vaccine, and the percentage of vaccines purchased at the public and private sector costs. Vaccine administration costs were calculated using the weighted average of the actual public and private sector administration costs for each vaccine and the percentage of vaccines administered at the public and private sector costs. Market shares for each vaccine were assumed to be the same as in the 2024 CDC CE model for the GSK MenABCWY vaccine. As in the aforementioned CDC CE model, we assumed no vaccine wastage due to administration errors in our analysis [29, 47].

Base Case Outcomes

Epidemiological outcomes included the annual number of IMD cases, IMD deaths, and occurrences of IMD sequelae by patient age and serogroup for each intervention or comparator strategy.

Economic outcomes included lifetime QALY losses for patients (due to acute IMD, IMD-related death, and long-term sequelae) and patients’ family and network (due to bereavement and care of patients with IMD in the acute phase and with long-term sequelae), with discounted life-years and QALYs also calculated to inform the economic component of the model. Costs included vaccination costs and total societal costs (i.e., costs associated with the health outcomes of each incident IMD case, including direct medical costs [acquisition, administration, and serious adverse events due to vaccination; IMD acute care costs; and costs due to IMD sequelae], direct nonmedical costs [special education costs], and indirect costs due to IMD [caregiving for patients with IMD by family and networks and market and nonmarket productivity losses for patients with IMD or their family members due to acute care, long-term sequelae, or premature death]).

Epidemiological and economic outcomes were then assessed across intervention and comparator strategies to determine PHI and CE. PHI outcomes of interest included cumulative IMD cases averted, IMD deaths averted, and QALY losses averted. The CE outcome of interest was the ICER of intervention versus comparator strategies, measured as incremental cost per QALY gained.

Analyses

Base Case Analysis

All base case results reflect cumulative outcomes for the entire US population in the years 2025–2039. The present analysis first explored intervention strategies that improved PHI versus SoC, then assessed associated costs, and finally, determined the CE of those strategies that improved PHI relative to SoC.

The PHI of each intervention strategy was calculated against NV and SoC options (SoC: Q-Q-B-B [routine MenACWY at ages 11 and 16 years and SCDM MenB at age 16 years and again 6 months later] and SoC: Q-P-B [routine MenACWY at age 11 years, SCDM MenABCWY at age 16 years, and SCDM MenB at age 16 years and 6 months]). The strategies that resulted in improved PHI versus SoC (i.e., more IMD cases averted, more deaths averted, and less QALYs lost) were subsequently evaluated to determine their total societal costs and total QALYs gained, and hence, their CE via ICERs.

Sensitivity Analyses

Deterministic sensitivity analyses (DSAs) were performed for schedule options that resulted in an improved PHI compared with SoC: Q-Q-B-B. DSAs were not performed versus SoC: Q-P-B due to uncertainties related to the recent introduction of pentavalent vaccines, which were addressed by scenario analyses. Only inputs for which ranges are specified were varied. All stratified inputs were varied together across stratifications (e.g., for inputs stratified by age, values applying to all ages were varied at once). The values were varied across reasonable ranges of upper and lower bounds while keeping all other parameters constant. Inputs with the largest impact on ICERs were sorted and arranged in descending order.

Probabilistic sensitivity analyses (PSAs) were also performed for schedule options that resulted in an improved PHI compared with SoC: Q-Q-B-B, to capture uncertainty in the estimates of incremental QALYs and incremental costs for intervention strategies versus the SoC. A Monte Carlo simulation with 500 iterations (found to be sufficient for the PSA to demonstrate convergence in the outcomes of interest) was used. Uncertainty in model parameters was assessed using probability distributions around corresponding base case values (Supplementary Table 2).

Scenario Analyses

Given the lack of available data regarding real-world vaccine coverage of the SoC: Q-P-B recommendation [20], conversion from the MenB to MenABCWY vaccine in the base case economic analysis assumed full (100%) coverage conversion from MenB to MenABCWY for Q-P-B and Q-P-P intervention strategies. Coverage conversion was defined as the utilization of P in place of B, and full (100%) coverage conversion indicated that P vaccines fully replaced B vaccines (e.g., 75% conversion would indicate that P vaccines accounted for 75% of MenB-containing vaccine coverage, while B vaccines accounted for the remaining 25%). However, challenges due to the lack of interchangeability between MenB-component vaccines originating from different manufacturers and corresponding HCP concerns about potential maladministration, and HCP uncertainty regarding the use of the MenABCWY vaccine outside of the indicated FDA 2-dose vaccine series, can be noted as factors potentially leading to lower conversion rates from B to P in Q-P-B intervention strategies in real-world practice [48, 49]. Therefore, a scenario analysis exploring lower conversion rates was conducted among intervention strategies, which improved PHI in the base case scenario to assess the effect of these real-world implementation considerations. Conversions of 50% from B to P in Q-P-B and 75% from B to P in Q-P-P were assumed on the basis of the expectation that conversion to P would be higher in Q-P-P due to increased HCP willingness to use P in that vaccine schedule, compared with a schedule for which both P and B would need to be stocked (Q-P-B).

Results

Base Case Analysis

Improvements in PHI

All intervention strategies improved PHI compared with NV over the 15-year time horizon (Supplementary Fig. 2). However, only intervention strategies under schedule options 1 (1a–f) and 2 (2a–f), which retained routine MenACWY at age 11 years, demonstrated improvements in PHI relative to SoC: Q-Q-B-B and SoC: Q-P-B. Under schedules 1 and 2, intervention strategies with a 0,6-month dose interval for MenB-containing vaccines averted 39 and 21 IMD cases, respectively, and strategies with a 0,24-month dose interval for MenB-containing vaccines averted 28 and 12 IMD cases, respectively (Fig. 2). The greater positive PHI with a 0,6-month dose interval is driven by higher estimated vaccination completion rates among those aged 16 versus 18 years.

Fig. 2.

US population IMD cases averted for intervention strategies versus SoC: Q-Q-B-B and SoC: Q-P-B, years 2025–2039. a 0,24-month dose interval for MenB-containing vaccines. b 0,6-month dose interval for MenB-containing vaccines. B MenB vaccine, IMD invasive meningococcal disease, MenB IMD caused by meningococcal bacteria serogroup B, Men meningococcal, N no vaccine given, NV no vaccination, P MenABCWY vaccine, Q MenACWY vaccine, SoC standard of care, US United States

Due to lower coverage and/or no protection against MenACWY at younger ages, intervention strategies under schedule options 3, 4, and 5 worsened PHI relative to both SoC: Q-Q-B-B and SoC: Q-P-B options.

In the intervention strategies that improved PHI versus SoC: Q-Q-B-B or SoC: Q-P-B (all strategies under schedules 1 and 2), no additional MenACWY cases were averted, with improvements in PHI driven by additional averted MenB cases (Supplementary Table 4). Deaths and QALY losses averted followed a similar pattern as IMD cases averted, with intervention strategies employing a 0,6-month dose interval for MenB-containing vaccines resulting in a greater positive PHI than those employing a 0,24-month dose interval (Supplementary Table 5).

Assessment of Costs

Intervention strategies Q-P-B (1c), Q-P-P (2b), and Q-P-B (2c) with a 0,24-month dose interval for MenB-containing vaccines and Q-P-P (2e) and Q-P-B (2f) with a 0,6-month dose interval for MenB-containing vaccines resulted in both lower vaccination and total societal costs compared with SoC: Q-Q-B-B (Supplementary Table 6). Q-P-B (1c), Q-P-P (2b), and Q-P-B (2c) with a 0,24-month dose interval for MenB-containing vaccines resulted in cost savings of $0.26 billion, $1.40 billion, and $1.61 billion, respectively, while Q-P-P (2e) and Q-P-B (2f) with a 0,6-month dose interval for MenB-containing vaccines produced cost savings of $0.27 billion and $0.60 billion, respectively (Fig. 3). The intervention strategies that displayed the highest PHI, Q-Q-B-B (1d), Q-P-P (1e), and Q-P-B (1f) with a 0,6-month dose interval for MenB-containing vaccines resulted in the largest reductions in both direct IMD-related costs and indirect costs but did not reduce total societal costs relative to SoC: Q-Q-B-B (Supplementary Table 6). Compared with SoC: Q-Q-B-B, all Q-Q-B-B intervention strategies (1a, 2a, 1d, and 2d) were associated with higher incremental total societal costs, as were Q-P-P strategies 1b and 1e, and Q-P-B strategy 1f (Fig. 3). However, all intervention strategies incorporating the MenABCWY vaccine (P) demonstrated lower incremental total societal costs compared with Q-Q-B-B intervention strategies within the same schedule option, which involve administration of individual MenACWY and MenB vaccines.

Fig. 3.

US population incremental total societal cost of intervention strategies with 0,24-month and 0,6-month dose intervals for MenB-containing vaccines under schedule options 1 and 2 versus SoC: Q-Q-B-B (a, b) and SoC: Q-P-B (c, d). a Versus Q-Q-B-B; 0,24-month dose interval. b Versus Q-Q-B-B; 0,6-month dose interval. c Versus Q-P-B; 0,24-month dose interval. d Versus Q-P-B; 0,6-month dose interval. B MenB vaccine, IMD invasive meningococcal disease, Men meningococcal, MenB IMD caused by meningococcal bacteria serogroup B, N no vaccine given, P MenABCWY vaccine, Q MenACWY vaccine, SoC standard of care, US United States

Compared with SoC: Q-P-B, all intervention strategies had lower direct IMD-related and indirect costs, but higher incremental total societal costs over 15 years (Supplementary Table 6). Intervention strategies Q-P-P (2b) and Q-P-B (2c) with a 0,24-month dose interval for MenB-containing vaccines and Q-P-P (2e) and Q-P-B (2f) with a 0,6-month dose interval for MenB-containing vaccines improved PHI while minimizing additional total societal costs compared with SoC: Q-P-B (Supplementary Table 6). While no cost-saving intervention strategies were identified compared with SoC: Q-P-B, cost reductions were observed among all Q-P-P and Q-P-B intervention strategies compared with those in the same schedule option with individual Q and B vaccines. The total incremental societal cost associated with Q-Q-B-B (1a) was $6.35 billion; Q-P-P (1b) and Q-P-B (1c) had total incremental societal costs of $2.35 billion and $2.07 billion, respectively, reducing incremental societal costs by more than $3.99 billion (63%) versus Q-Q-B-B (1a). Similarly, Q-P-P (2e) and Q-P-B (2f) reduced total incremental societal costs by more than $2.77 billion each (57%) versus Q-Q-B-B (2d; Fig. 3).

When assessing the costs of intervention strategies, increasing vaccination coverage (e.g., routine or risk-based recommendations for MenB-containing vaccines; Table 1; Supplementary Table 6) resulted in greater vaccination costs in some cases. However, reduced direct IMD-related and indirect costs were observed among all intervention strategies, while incorporating the MenABCWY vaccine (P) led to cost savings in some strategies (1c, 2b, 2c, 2e, and 2f versus SoC: Q-Q-B-B).

CE Results

Given that increased coverage for strategies with a 0,6-month dose interval for MenB-containing vaccines drove higher vaccination costs, the ICERs for these strategies were generally higher than for strategies with a 0,24-month dose interval for MenB-containing vaccines (Supplementary Fig. 3). Irrespective of this trend, the Q-P-P (2e) and Q-P-B (2f) strategies with a 0,6-month dose interval for MenB-containing vaccines displayed cost-saving ICERs compared with SoC: Q-Q-B-B, indicating both lower costs and increased QALYs. No cost-saving ICERs were observed for any comparison versus SoC: Q-P-B over 15 years.

Sensitivity and Scenario Analyses

Sensitivity Analyses

The top inputs driving the ICER outcomes for Q-P-B- and Q-P-P-related intervention strategies appeared frequently across all DSAs. Five inputs appeared in the top ten in all DSAs: vaccine price of the GSK MenABCWY vaccine, vaccine coverage for the GSK MenABCWY vaccine (first dose), discount rate for outcomes, discount rate for costs, and vaccine effectiveness for the MenB component (first dose) of MenB-containing vaccines (i.e., MenB and MenABCWY). Under schedule option 1 (routine recommendations for Q and B/P vaccines), when the lower bound for vaccine coverage for the GSK MenABCWY vaccine (first dose) was used, the estimated QALYs lost were greater than for SoC: Q-Q-B-B (i.e., fewer IMD cases averted than SoC). This finding contrasted with the base case, where fewer QALYs were lost with schedule option 1. Overall, results were robust to a wide range of uncertainties in key parameters that influenced the ICERs of the intervention strategies. For example, the DSAs found that strategies 1c, 2b, and 2c remained cost-saving versus SoC: Q-Q-B-B, regardless of the lower or upper bound values for the majority of parameters.

On the basis of samples of 500 iterations each, health outcomes estimates in the PSAs were consistent with the base case analyses, with a greater number of estimated QALY losses averted within 95% credible intervals versus SoC: Q-Q-B-B for strategies 1b, 1c, 2b, 2c, 1e, 1f, 2e, and 2f (Supplementary Fig. 4). Cost outcomes were also generally consistent with the base case analyses, with strategies 1c, 2b, 2c, 2e, and 2f estimated to be cost-saving within credible intervals versus SoC: Q-Q-B-B; the 95% credible interval for schedule 1b (Q-P-P) included cost savings versus SoC: Q-Q-B-B (mean [95% credible interval] incremental costs in $ billion: $0.03 [− $0.07–$0.14]; Supplementary Fig. 5).

Scenario Analysis

PHI results were consistent with the base case when considering lower conversion rates from MenB [B] to MenABCWY [P] vaccines, as total population coverage and clinical characteristics of the MenB component of MenB-containing vaccines were assumed to remain the same regardless of the rate of conversion to P. Within each schedule option, the lowest costs were observed with Q-P-P intervention strategies, followed by Q-P-B intervention strategies, compared with SoC: Q-Q-B-B, regardless of dose interval for MenB-containing vaccines (Table 3). The highest cost savings were associated with strategies Q-P-P (2b) and Q-P-B (2c) with a 0,24-month dose interval for MenB-containing vaccines versus SoC: Q-Q-B-B ($0.68 billion and $0.06 billion, respectively; Table 3).

Table 3.

Scenario analysis for lower conversion rate from MenB to MenABCWY vaccine: US population IMD cases averted and incremental total societal costs for intervention strategies under schedule options 1 and 2 versus SoC: Q-Q-B-B and SoC: Q-P-B, years 2025–2039

Outcomes	0,24-month dose interval between MenB-containing vaccines						0,6-month dose interval between MenB-containing vaccines
	Schedule option 1: Qroutine at ages 11 and 16 years, Broutine with first dose at age 16 years and second at age 18 years			Schedule option 2: Qroutine at ages 11 and 16 years, Brisk-based with first dose at age 16 years and second at age 18 years			Schedule option 1: Qroutine at ages 11 and 16 years, Broutine with first dose at age 16 years and second at age 16 years and 6 months			Schedule option 2: Qroutine at ages 11 and 16 years, Brisk-based with first dose at age 16 years and second at age 16 years and 6 months
	Q-Q-B-B (1a)	Q-P-P (1b)	Q-P-B (1c)	Q-Q-B-B (2a)	Q-P-P (2b)	Q-P-B (2c)	Q-Q-B-B (1d)	Q-P-P (1e)	Q-P-B (1f)	Q-Q-B-B (2d)	Q-P-P (2e)	Q-P-B (2f)
Total IMD cases averted	28	28	28	12	12	12	39	39	39	21	21	21
Incremental total societal costs ($ in billion) versus SoC: Q-Q-B-B	$4.02	$1.03	$1.88	$1.49	− $0.68	− $0.06	$5.41	$2.54	$3.27	$2.49	$0.42	$0.95
Incremental total societal costs ($ in billion) versus SoC: Q-P-B	$5.90	$2.91	$3.76	$3.37	$1.20	$1.82	$7.29	$4.42	$5.15	$4.37	$2.30	$2.82

Results reflect recommendation types for intervention strategies (under schedule options), with negative numbers indicating improved incremental costs versus the comparator of interest

B, MenB vaccine; IMD, invasive meningococcal vaccine; Men, meningococcal; MenACWY, IMD caused by meningococcal bacteria serogroups A, C, W, and Y; MenB, IMD caused by meningococcal bacteria serogroup B; P, MenABCWY vaccine; PHI, public health impact; Q, MenACWY vaccine; SoC, standard of care

Discussion

The evaluation of proposed options to revise the adolescent meningococcal vaccine schedule presents an opportunity to identify intervention strategies that both improve PHI and minimize costs versus the SoC options. Notably, five intervention strategies (Q-P-B [1c], Q-P-P [2b], and Q-P-B [2c] with a 0,24-month dose interval for MenB-containing vaccines, and Q-P-P [2e] and Q-P-B [2f] with a 0,6-month dose interval for MenB-containing vaccines) improved PHI and were cost-saving relative to SoC: Q-Q-B-B (i.e., the standard of care schedule that did not implement any MenABCWY vaccines), averting between 12 and 28 IMD cases and producing cost savings ranging from $0.26 billion to $1.61 billion over 15 years (approximately $0.02 billion to $0.11 billion annually).

In this analysis, all evaluated intervention strategies resulted in improvements in PHI versus NV over the 15-year time horizon. However, only intervention strategies that retained the MenACWY vaccine for those aged 11 years (under schedule options 1 and 2) displayed improvements in PHI compared with the SoC schedules. A 2005 study highlighted the importance of routine MenACWY vaccination in those aged 11–12 years, with IMD cases and deaths averted and direct disease and productivity loss costs reduced [38]. Langevin et al. and Shoukat et al. both built upon these findings, indicating that administration of the MenACWY vaccine among those aged 11 years remains critical; waiting to administer the first MenACWY among those aged 16 years, as opposed to those aged 11 years, would likely result in additional IMD cases and IMD-related deaths [50, 51]. In addition to the potential increase in IMD cases and deaths, Shaw et al. considered the wider public health impacts of removing the routine MenACWY vaccination for those aged 11–12 years, including the potential for reduced insurance coverage, exacerbating existing vaccine affordability and access disparities [52].

While reported IMD incidence rates in the 11–12 year age group are currently low, meningococcal carriage rates are thought to increase throughout childhood and peak in adolescents, suggesting that these low incidence rates may in fact be indicative of the impact of vaccination coverage, rather than low risk of acquisition [53]. Further, adolescents aged 11–12 years typically receive several vaccines during standard healthcare preventive visits, as encouraged by the American Academy of Pediatrics (AAP), the American Academy of Family Physicians (AAFP), and the American Medical Association (AMA) since 1996. As such, existing guidelines from professional organizations facilitate administration of the primary MenACWY dose [54].

Additionally, intervention strategies utilizing a 0,6-month dose interval for MenB-containing vaccines (the dosing interval approved by the FDA) had the greatest positive PHI in terms of IMD cases averted, deaths averted, and QALY losses minimized. Due to more frequent interactions with the healthcare system among younger patients, vaccination coverage rates were assumed to be higher in 0,6-month dose intervals relative to 0,24-month dose intervals for MenB-containing vaccines, resulting in improved PHI for the 0,6-month schedules. A 2019 CDC report concluded that the proportion of individuals attending preventive care office visits peaks among those aged < 18 years (32%) and decreases among those aged 18–64 years (24%), indicating that earlier administration of the booster MenABCWY/MenB vaccine dose may be beneficial for coverage [55]. Further, a 2022 retrospective analysis of US health insurance claims databases found that 57.1% of those aged 16 years reported ≥ 1 well-child or preventative care visit compared with 39.0% among those aged 19 years. The frequency of these HCP visits continued to decrease year-on-year over the observed age range, emphasizing the importance of initiating preventative interventions at younger ages [56]. While strategies utilizing a 0,6-month dose interval for MenB-containing vaccines tended to be less cost-effective than those utilizing a longer dose interval, the Q-P-P (2e) and Q-P-B (2f) strategies utilizing the 0,6-month dose interval reported cost savings compared with SoC: Q-Q-B-B.

Intervention strategies under schedule option 1, which employed routine recommendations for both MenACWY and MenB/MenABCWY vaccines, averted the greatest number of IMD cases, particularly when considering a 0,6-month dose interval for MenB-containing vaccines. As proposed by the CDC, target populations for risk-based recommendations (utilized under schedule option 2 for MenB-containing vaccines) include adolescents planning to attend college or those in congregate living situations (e.g., foster care, boarding school, correctional facilities) who are at higher risk of MenB acquisition [30, 57, 58]. In addition to schedule option 2 averting fewer IMD cases than schedule option 1 in this model, the emphasis placed on college attendance for administration of the risk-based vaccine highlights important equity considerations. While college students may face a heightened risk of MenB acquisition, a 2022 report from the CDC found that non-college-attending adolescents made up more than 29% of MenB cases among those aged 18–24 years, but this population would potentially be excluded from risk-based recommendations [11, 57, 58]. The exclusion of non-college-attending individuals may systematically disadvantage particular racial groups or individuals of a lower socioeconomic status, as these populations are less likely to attend college at the national level [59]. Further, there may be implementation challenges associated with schedule options that recommend risk-based vaccines at 16 years of age, as decisions regarding college attendance may still be uncertain at that time.

Compared with NV, intervention strategies under schedule options 1 and 2 resulted in incremental societal costs, mainly driven by vaccination costs, but these costs were partially offset by reductions in both direct IMD-related costs and indirect costs. When comparing the intervention strategies under schedule options 1 and 2 versus SoC: Q-Q-B-B, increased coverage almost always led to increased vaccination costs. However, several intervention strategies involving the use of MenABCWY vaccines were cost-saving compared with SoC: Q-Q-B-B, which does not include MenABCWY. No intervention strategies under schedule options 1 and 2 resulted in overall cost savings versus SoC: Q-P-B (due to higher vaccination costs), but all exhibited lower total IMD disease costs and IMD indirect costs than SoC: Q-P-B. Intervention strategies that incorporated the MenABCWY vaccine also displayed lower societal costs relative to Q-Q-B-B intervention strategies under the same schedule options, driven by lower vaccination costs associated with schedules containing the MenABCWY vaccine compared with those using individual MenACWY and MenB vaccines. As such, incorporating the MenABCWY vaccine into an updated vaccination schedule may facilitate improved PHI, while partially or entirely offsetting associated costs in real-world practice.

The scenario analysis, which evaluated a lower conversion rate from the MenB to MenABCWY vaccine, highlighted the importance of considering practical implementation feasibility in revising the adolescent meningococcal vaccine schedule. Although MenB-containing vaccines originating from different manufacturers in real-world practice may increase vaccine options for HCPs, current MenB-containing vaccines administered as part of a two-dose series must originate from the same manufacturer (i.e., lack of interchangeability) [60]. Thus, potential for maladministration should be considered as part of the implementation feasibility of Q-P-B strategies, possibly exacerbated by imperfect immunization history tracking. Further, HCPs’ hesitation in using the MenABCWY vaccine outside of the FDA-indicated two-dose series may lead to lower acceptance of the Q-P-B strategy, as modeled in the scenario analysis. As implementation challenges may reduce the cost-minimizing potential of MenABCWY, strategies that simplify implementation and facilitate greater conversion between MenB-containing vaccines (i.e., utilizing a Q-P-P schedule) may be more likely to minimize costs than Q-P-B strategies.

In line with the findings of this analysis, a 2023 CDC evaluation indicated that while most MenABCWY vaccine strategies would result in higher costs per QALY compared with SoC, the Q-P-B strategy could be incrementally cost-saving [37]. Furthermore, a 2025 CE analysis of the GSK MenABCWY vaccine found that both Q-P-P and Q-P-B strategies resulted in cost savings compared with Q-Q-B-B, with improved PHI observed with Q-P-P and the most favorable cost-effectiveness associated with Q-P-B [29]. While aligned with the favorable economic outcomes associated with implementation of the MenABCWY vaccine, it should be noted that the CE analysis conducted by Dong et al. found higher ICERs for certain comparisons than the present analysis [29]. This discrepancy is likely due to utilization of more recent incidence data to reflect IMD rates prior to vaccine introduction (resulting in a lower number of cases, as IMD incidence has generally declined over time). In contrast to our findings, a recently published analysis by Shin et al. evaluating the PHI and CE of possible changes to the US adolescent meningococcal vaccination schedule suggested that Q-Q-B-B is the most cost-effective schedule under consideration, with Q-P-B and Q-P-P resulting in additional costs and higher ICERs [61]. Differences in findings for Shin et al. and those reported in our analysis and the 2024 CDC evaluation likely stem from differing vaccine coverage rates considered in the models. Indeed, Shin et al. assumed full replacement of MenACWY with MenABCWY and substantially higher coverage for MenB-containing vaccine doses than our analysis and the CDC analysis. Despite these differences, both Shin et al. and our analysis estimated that removing the first dose of MenACWY at ages 11–12 years would negatively impact public health.

Limitations

IMD incidence among unvaccinated individuals for all types of vaccine recommendations within the model (routine, SCDM, and risk-based) were assumed to be the same in base case analyses. However, as patients vaccinated under a risk-based strategy may have a higher risk of IMD acquisition, this assumption may have underestimated the number of IMD cases averted through risk-based MenB vaccination. No carriage effects or effects on the severity of IMD breakthrough cases in vaccinated individuals due to cross-protection were applied, despite some available data suggesting that vaccines aimed at preventing IMD cases due to serogroups A, C, W, and Y can also protect against meningococcal carriage of some serogroups, and that vaccines aimed at preventing IMD due to serogroup B can provide cross-protection against IMD due to other serogroups [62–64]. Excluding the impact of vaccination on carriage protection from consideration in the model may have affected the apparent cost-effectiveness of certain vaccine strategies; however, this methodological choice was made in light of existing uncertainties regarding the effect of vaccination on meningococcal carriage. While the inclusion of effects of vaccination on meningococcal carriage would increase the PHI and economic favorability of all vaccination strategies relative to no vaccination, the impact of these effects on the comparative CE of the strategies would depend on differences in age-specific vaccination coverage across scenarios, age patterns in carriage prevalence, the targeted serogroups susceptible to carriage protection, and other factors.

In line with other meningococcal disease models, this model assumed static and steady-state IMD incidence over the analysis period [28, 65]. However, IMD incidence may not have been steady prior to 2005, when IMD vaccinations were introduced, nor has incidence remained steady since. For this reason, there was uncertainty around the incidence data included within the model. Estimates were obtained from publicly available CDC data for serogroups C, W, and Y from 1996 to 2005 and serogroup B from 1994 to 2013. These longer periods of pre-vaccine era data (as opposed to the 2-year data [2003−2005 for MenACWY and 2012−2014 for MenB] utilized by the 2024 CDC model) [29] better capture the unpredictability of the disease over a more expansive time range [37].

Despite no available clinical trial data supporting a 0,24-month dose interval for Men-B containing vaccines, vaccine effectiveness for these strategies was assumed equal to the comparable effectiveness of the 0,6-month dose interval. Particular IMD sequelae were informed by data that were not IMD-specific, when limited data were available. However, no data currently suggest that the cause of sequelae (e.g., IMD versus other diseases) changes the severity/impact of the sequelae. These assumptions were further validated by expert clinical opinion [8]. Due to a lack of data availability, the assumed short duration of events, and the absence of lifelong effects, no QALY losses due to vaccine-related serious adverse events were included in the model. This assumption was consistent with other IMD-related economic models but may have underestimated the QALY-related impact of vaccination under strategies that increased population-level coverage against serogroups A, B, C, W, and Y compared with SoC recommendations [29, 37, 38, 57, 58, 66–70].

Real-world coverage data were not available for SoC: Q-P-B. Therefore, intervention strategy (and SoC: Q-P-B) coverage was estimated on the basis of SoC: Q-Q-B-B coverage and adjusted for intervention strategies with a 0,24-month dose interval for MenB-containing vaccines on the basis of healthcare visit patterns among adolescents and young adults. All vaccinations were assumed to occur within the context of healthcare visits rather than other settings, such as schools, health departments, or student centers. IMD outbreaks were not modeled explicitly, but only considered in terms of costs related to public health responses. Considering the tests of uncertainty inherent to the multiplicity of the 27 intervention strategies in base case analyses, no PSA was conducted for the schedule revisions. PSAs were conducted by Shah et al. to evaluate uncertainty around the model’s QALY estimates versus SoC, finding that, similar to the base case results, more QALY losses were averted with a Q-P-P schedule implementing routine recommendations for all vaccines versus SoC [28]. However, DSAs were conducted, with vaccine price of the GSK MenABCWY vaccine, vaccine coverage for the GSK MenABCWY vaccine (first dose), discount rate for outcomes, discount rate for costs, and vaccine effectiveness for the MenB component (first dose) found to have the largest impact on ICER outcomes.

In January 2026, the CDC recommendations for the MenACWY doses at ages 11–12 years and 16 years were changed from a routine recommendation to SCDM [15, 16]; as of the time of this study, other recommending organizations (e.g., AAP) have maintained a routine recommendation for MenACWY vaccination in adolescents [71]. Routine recommendations for these doses were considered the standard of care in our analyses as they represented the CDC recommendations at the time of the analyses [12, 13]. While our analyses did not estimate outcomes for schedule options with SCDM recommendations for MenACWY, such options would have had lower vaccination coverage rate assumptions for MenACWY compared with coverage rate assumptions for a routine recommendation and thus likely would negatively impact public health outcomes [19]. Regardless of the updated CDC recommendations, the findings presented here remain applicable and important for organizations aiming to assess the PHI and CE of adolescent meningococcal vaccination schedule options.

Conclusions

This analysis evaluated the PHI and CE of potential revisions to the adolescent meningococcal vaccine schedule. Strategies that retained routine MenACWY vaccination among those aged 11–12 years and included a routine or risk-based recommendation for MenB-containing vaccines among those aged 16 years improved PHI versus each SoC schedule, particularly when utilizing a 0,6-month dose interval for MenB-containing vaccines. Further, five strategies that incorporated MenABCWY resulted in cost savings versus the SoC schedule that does not utilize MenABCWY, suggesting that incorporating the pentavalent vaccine could improve public health while fully offsetting costs. The demonstrated benefit of retaining routine MenACWY at age 11–12 years in the adolescent meningococcal vaccine schedule, while simplifying the schedule by incorporating MenABCWY in place of separate MenACWY and MenB vaccines at age 16–23 years, presents a tremendous opportunity to improve PHI in a cost-effective manner, minimizing the humanistic and economic burden of this devastating and unpredictable disease.

Supplementary Information

Below is the link to the electronic supplementary material.

Funding

This study was sponsored by GSK ID: VEO-001202. Support for third-party writing assistance for this article, provided by Brody Mayoras, Costello Medical, US was funded by GSK in accordance with Good Publication Practice (GPP 2022) guidelines (https://www.ismpp.org/gpp-2022).

Declarations

Disclosures

OHR is employed by and holds financial equities in GSK; GJ received consulting fees from GSK; JG is employed by RTI Health Solutions, which was paid by GSK to conduct this study; JC is employed by and holds financial equities in GSK; MG is employed by RTI Health Solutions, which was paid by GSK to conduct this study; ZK is employed by and holds financial equities in GSK; DEC is employed by and held financial equities in GSK at the time of the study and is now employed by Johnson & Johnson; CB is employed by GSK and holds financial equities in GSK and Pfizer; AA is employed by and holds financial equities in GSK; and HS is employed by and holds financial equities in GSK.

Data Sharing Statement

The data generated during and/or analyzed during the current study are available within the paper and its Supplementary Information. Additional data may be requested from the corresponding author, as reasonable.

Author Contributions

Substantial contributions to study conception and design: OHR, GJ, JG, ZK, DEC, CB, and HS; substantial contributions to analysis and interpretation of the data: OHR, GJ, JG, JC, MG, ZK, DEC, CB, AA, and HS; drafting the article or revising it critically for important intellectual content: OHR, GJ, JG, JC, MG, ZK, DEC, CB, AA, and HS; and final approval of the version of the article to be published: OHR, GJ, JG, JC, MG, ZK, DEC, CB, AA, and HS.