Invasive meningococcal disease, caused by the bacterium Neisseria meningitidis, is life-threatening but can be prevented with vaccination. There are effective vaccines against different meningococcal serogroups, including serogroup B. Evidence from immunization programs with the 4-component meningococcal serogroup B vaccine, 4CMenB, over the last decade confirms its effectiveness and positive impact against serogroup B disease in people of all age groups. To assess the performance of serogroup B vaccines in clinical trials, tests are required that take into account the wide diversity of serogroup B strains circulating in the population. In this study, the performance of 4CMenB was evaluated using the enc-hSBA assay, which uses the complement (proteins) present in each vaccinated person’s blood, and is used to test a large number of N. meningitidis strains, thereby determining breadth of immune response, based on the vaccine’s killing activity against diverse strains. Using this assay, our results showed breadth of immune response following administration of 4CMenB (two doses, two or six months apart) against the 110 serogroup B strains tested that was consistent with its performance in immunization programs, with no additional benefit from administering three 4CMenB doses over the six-month period. The safety of 4CMenB was consistent with its known safety profile.

Background/Objectives: Meningococcal disease is primarily caused by serogroups A, B, C, W, and Y. Current US vaccination recommendations include routine serogroup A/C/W/Y (MenACWY) vaccination (ages 11–12 and 16 years) and a two-dose, 0-, 6-month MenB vaccination series (age 16–23 years) based on shared clinical decision-making. Administration of the first-in-class Pfizer pentavalent MenABCWY vaccine (Penbraya^TM), which received US licensure in 2023 as a two-dose, 0-, 6-month series, is endorsed when the MenACWY and MenB vaccines are recommended at the same visit. This study evaluated the immunogenicity and safety of two extended two-dose schedules of MenABCWY in healthy adolescents. Methods: In this observer-blinded, phase 2b study (ClinicalTrials.gov, NCT04440176; 19 June 2020), 309 healthy 11- to 14-year-olds were randomized 1:1 to receive a 0-, 36-month or 0-, 12-month Pfizer MenABCWY schedule, which more closely aligns with current US MenACWY vaccination recommendations. Endpoints included serum bactericidal assay using human complement seroprotection rates (titers ≥ 1:8 or ≥1:16, depending on strain), seroresponse rates (≥4-fold increase from baseline titer), and geometric mean titers (GMTs). Safety was also assessed. Results: One month after the second Pfizer MenABCWY dose, serogroup A/B/C/W/Y seroprotection rates were 100% for the 0-, 36-month schedule and 96.6–100% for the 0-, 12-month schedule; seroresponse rates were 100% and 92.9–100%, respectively. GMTs generally trended higher with the 0-, 36-month schedule. Seroprotection rates through 24 months after the second dose of the 0-, 12-month schedule were 44.0–75.0% for serogroup B and 88.9–100% for serogroup A/C/W/Y). No safety issues were identified. Conclusions: These data support Pfizer MenABCWY dosing flexibility and utility within the current or possible future US meningococcal vaccination framework.