A Booster Response to an Investigational Meningococcal MenABCWY Vaccine in Adolescents Previously Vaccinated with MenACWY, 4CMenB or MenABCWY: a Phase 2, Observer-Blind, Placebo-Controlled, Randomized Study

Background: The MenABCWY vaccine combines antigens against the 5 serogroups of N. meningitidis responsible for most cases of meningococcal disease globally. Previously we studied the immunogenicity of 2 doses (0,2 months schedule) of MenABCWY in adolescents compared to 4CMenB and Placebo/MenACWY (NCT01272180). This study evaluated antibody persistence 2 years after primary vaccination, and response to a MenABCWY booster dose (NCT01992536).

Methods: 194 adolescents who had participated in the primary study were enrolled and vaccinated. Antibodies against serogroups A, B, C, W and Y were measured by serum bactericidal assay with human complement (hSBA). Safety was assessed by frequencies of solicited and unsolicited adverse events (AEs).

Results: At 2 years after the primary vaccination series, 27%, 29% and 31% of MenABCWY, 4CMenB and Placebo/MenACWY vaccinees, respectively, had hSBA titers ≥8 against serogroup A; 67%, 45% and 57% against serogroup C; 92%, 76% and 68% against serogroup W and 65%, 16% and 46% against serogroup Y. One month after the MenABCWY booster dose, 96% of MenABCWY, 100% of 4CMenB and 84% of Placebo/MenACWY vaccinees demonstrated seroresponses against serogroup A, 85%, 100% and 95% against serogroup C, 85%, 82% and 83% against serogroup W and 96%, 73% and 95% against serogroup Y. At 2 years post-vaccination, percentages of subjects with hSBA titers ≥5 against the 4 serogroup B test strains were 24%–35% for NadA in the MenABCWY and 4CMenB groups vs 7% in the Placebo/MenACWY group, 37%–50% vs 22% for NHBA, 26%–29% vs 14% for fHbp and 16%–24% vs 3% for PorA, respectively. One month after the MenABCWY booster dose, percentages of subjects with hSBA titers ≥5 across strains increased to 82%–100% in the MenABCWY and 4CMenB groups, and to 19%–35% in the Placebo/MenACWY group. The most frequent solicited AEs were injection site pain (77%–100% across groups), fatigue (35%–52%), and headache (27%–57%).

Conclusion: Antibody persistence was substantial for most vaccine antigens 2 years after primary vaccination. A MenABCWY booster dose elicited robust immune responses to serogroups ACWY in adolescents previously vaccinated with MenABCWY, 4CMenB and Placebo/MenACWY, and to serogroup B strains in subjects who previously received MenABCWY or 4CMenB.

Funding: GlaxoSmithKline Biologicals SA