Assessing the impact of revising MenACWY vaccination schedule for adolescents in the United States: a modelling study.

Background: The current recommendation for MenACWY vaccination against invasive meningococcal disease (IMD) in the United States (US) includes two doses: the first dose at ages 11-12 and a booster dose at age 16. The Advisory Committee on Immunization Practices has proposed options for revising this schedule by either eliminating the first dose or adjusting the timing of the first dose to age 15 and the booster to ages 17-18. The impact of these alternative schedules on IMD incidence remains undetermined.

Methods: We developed an age-stratified, agent-based Monte-Carlo simulation model of meningococcal transmission dynamics, parameterised with US age demographics, to assess the impact of the proposed changes to the MenACWY vaccination schedules. Excluding serogroup A, absent in the US for decades, the model included serogroups C, W, and Y for asymptomatic infection (carriage) and vaccine effectiveness against IMD. We calibrated serogroup-specific transmission and IMD development probabilities by fitting the model to reported IMD cases from 1997 to 2004, before vaccine introduction. The calibrated model then simulated the current vaccination schedule (CVS) starting in 2005 and alternative schedules from January 1, 2025 to December 31, 2035, comparing outcomes over the same period.

Findings: Switching from the CVS to a single-dose program at age 16 with 61% vaccine uptake (as reported for the booster in 2022) would result in 1062 (95% Uncertainty Range [UR]: 724-1419) additional IMD cases during the 11-year study period. With a case fatality rate of 14.5%, this change could cause an estimated 154 (95% UR: 105-206) additional deaths. Even if vaccine uptake increased to 90% at age 16, the program would still result in 934 (95% UR: 640-1242) additional cases and 135 (95% UR: 93-180) more deaths compared to the CVS. The second alternative schedule (i.e. first dose at age 15, booster at ages 17-18) also increased IMD cases, notably shifting a substantial burden to adolescents aged 11-15 years.

Interpretation: Our findings indicate that the current MenACWY vaccination program remains more effective than the proposed alternatives, even with increased vaccine uptake during late adolescence. Improving the uptake rate of the booster at age 16 while maintaining the 11-12-year dose within the existing program would reduce the IMD burden among high-risk adolescents and young adults.

Funding: This study was in part supported by Sanofi. Seyed M. Moghadas acknowledges support from the Natural Sciences and Engineering Research Council of Canada Discovery Grant and Alliance Grant (ALLRP 576914-22). Alison P. Galvani acknowledges support from The Notsew Orm Sands Foundation.