Four-year antibody persistence and response to a booster dose of a pentavalent MenABCWY vaccine administered to healthy adolescents and young adults

Abstract

This open-label, multicenter extension study (NCT02451514) assessed persistence of Neisseria meningitidis serogroups ABCWY antibodies 4 years after primary vaccination. Adolescents and young adults who previously received 2 doses of MenABCWY+OMV (Group III), 1 dose of MenACWY-CRM (Group VI), or newly-recruited vaccine-naïve participants (Group VII) were administered 1 (Group III) or 2 doses (Groups VI and VII) of MenABCWY+OMV, 1 month apart. Immunogenicity was assessed by human serum bactericidal assay (hSBA). Safety and reactogenicity were also evaluated. Percentages of participants with hSBA titers ≥8 (serogroups ACWY), ≥5 (serogroup B) and hSBA geometric mean titers (GMTs) were evaluated in all 129 enrolled participants (Group III: 33; Group VI: 46; Group VII: 50). Anti-ACWY antibody concentrations waned over 4 years post-vaccination, but remained above pre-vaccination concentrations. Similarly, levels of antibodies against serogroup B test strains also waned over 4 years post-vaccination, but remained above pre-vaccination concentrations for some strains. MenABCWY+OMV booster induced a robust anamnestic anti-ACWY response in Group III and VI and a good response against serogroup B test strains (≥82%) in Group III. In serogroup B-naïve participants (Groups VI and VII), anti-B responses to 2 doses of MenABCWY+OMV were less homogenous and lower than in Group III. MenABCWY+OMV was reactogenic, but well-tolerated. No safety concerns were identified. These findings indicate that although antibodies against N. meningitidis serogroups ABCWY waned over 4 years post-vaccination, exposure to a MenABCWY+OMV booster dose elicits an anamnestic response in adolescents previously exposed to the same or another multivalent meningococcal vaccine.

Keywords: MenABCW; MenACWY; antibody persistence; booster dose; meningococcal vaccine.

Figure 1.

Focus on the patient section.

Figure 2.

Flow of participants Footnote: Primary study: participants received 1 or 2 doses of vaccine; Extension study 1: Follow-on participants for 10 months persistence, 3^rd dose administration (with control vaccination); Extension study 2: Follow-on participants for 4 years persistence, 3rd dose administration (with control vaccination). Group III; participants received 2 doses of MenABCWY+OMV (presented in this figure, for primary and extension 1 studies, as MenACWY-CRM + rMenB+OMV) in the primary study and 1 dose of MenABCWY+OMV in the extension study presented here (4 years post-primary study). Group VI; participants received 1 dose of MenACWY-CRM in the primary study and 2 doses, 1 month apart, of MenABCWY+OMV in the extension study presented here (4 years post-primary study). Group VII; participants were newly recruited and naïve to vaccination against A, B, C, W and Y serogroups of N. meningitidis. They were vaccinated with 2 doses, 1 month apart, of MenABCWY+OMV in the extension study presented here.

Figure 3.

Percentages of participants with hSBA ≥8 against serogroups A, C, W, and Y (a) and hSBA ≥5 against serogroup B (c) and hSBA geometric mean titers against serogroups A, C, W and Y (b) and serogroup B (d) at day 1 (FAS Persistence) Footnote: FAS, full analysis set; hSBA, human serum bactericidal assay, GMT, geometric mean titer; CI, confidence interval. Group III; participants received 2 doses of MenABCWY+OMV in the primary study and 1 dose of MenABCWY+OMV in the extension study presented here (4 years post-primary study). Group VI; participants received 1 dose of MenACWY-CRM in the primary study and 2 doses, 1 month apart, of MenABCWY+OMV in the extension study presented here (4 years post-primary study). Group VII; participants were newly recruited and naïve to vaccination against A, B, C, W and Y serogroups of N. meningitidis. They were vaccinated with 2 doses, 1 month apart, of MenABCWY+OMV in the extension study presented here. The group description in the legend includes all doses administered in the primary and extension studies.

Figure 4.

Percentages of participants with hSBA ≥8 against serogroups A, C, W, and Y (a) and hSBA ≥5 against serogroup B (c) and hSBA geometric mean titers by serogroups A, C, W and Y (b) and serogroup B (d) pre-vaccination and at day 31 post-vaccination (FAS Day 31) Footnote: FAS, full analysis set; hSBA, human serum bactericidal assay; GMT, geometric mean titer; CI, confidence interval. Group III; participants received 2 doses of MenABCWY+OMV in the primary study and 1 dose of MenABCWY+OMV in the extension study presented here (4 years post-primary study). Group VI; participants received 1 dose of MenACWY-CRM in the primary study and 2 doses, 1 month apart, of MenABCWY+OMV in the extension study presented here (4 years post-primary study). Group VII; participants were newly recruited and naïve to vaccination against A, B, C, W and Y serogroups of N. meningitidis. They were vaccinated with 2 doses, 1 month apart, of MenABCWY+OMV in the extension study presented here. The figure presents results of pre- and post-booster/first dose. The group description in the legend includes all doses administered in the primary and extension studies.