Long-term immunogenicity and safety after a single dose of the quadrivalent meningococcal serogroups A, C, W, and Y tetanus toxoid conjugate vaccine in adolescents and adults: 5-year follow-up of an open, randomized trial

Charissa Fay Corazon Borja-Tabora, Cecilia Montalban, Ziad A Memish, Dominique Boutriau, Devayani Kolhe, Jacqueline M Miller, Marie Van der Wielen, Charissa Fay Corazon Borja-Tabora, Cecilia Montalban, Ziad A Memish, Dominique Boutriau, Devayani Kolhe, Jacqueline M Miller, Marie Van der Wielen

Abstract

Background: Long-term protection against meningococcal disease is associated with persistence of post-vaccination antibodies at protective levels. We evaluated the bactericidal antibody persistence and safety of the quadrivalent meningococcal serogroups A, C, W and Y tetanus-toxoid conjugate vaccine (MenACWY-TT) and the meningococcal polysaccharide serogroups A, C, W, and Y vaccine (MenACWY-PS) up to 5 years post-vaccination.

Methods: This phase IIb, open, randomized, controlled study conducted in the Philippines and Saudi Arabia consisted of a vaccination phase and a long-term persistence phase. Healthy adolescents and adults aged 11-55 years were randomized (3:1) to receive a single dose of MenACWY-TT (ACWY-TT group) or MenACWY-PS (Men-PS group). Primary and persistence results up to 3 years post-vaccination have been previously reported. Antibody responses against meningococcal serogroups A, C, W, and Y were assessed by a serum bactericidal antibody assay using rabbit complement (rSBA, cut-off titers 1:8 and 1:128) at Year 4 and Year 5 post-vaccination. Vaccine-related serious adverse events (SAEs) and cases of meningococcal disease were assessed up to Year 5.

Results: Of the 500 vaccinated participants, 404 returned for the Year 5 study visit (Total Cohort Year 5). For the Total Cohort Year 5, 71.6-90.0 and 64.9-86.3 % of MenACWY-TT recipients had rSBA titers ≥1:8 and ≥1:128, respectively, compared to 24.8-74.3 and 21.0-68.6 % of MenACWY-PS recipients. The rSBA geometric mean titers (GMTs) remained above the pre-vaccination levels in both treatment groups. Exploratory analyses suggested that both rSBA GMTs as well as the percentages of participants with rSBA titers above the cut-offs were higher in the ACWY-TT than in the Men-PS group for serogroups A, W and Y, with no apparent difference for MenC. No SAEs related to vaccination or cases of meningococcal disease were reported up to Year 5.

Conclusion: These results suggest that a single dose of MenACWY-TT could protect at least 72 % of vaccinated adolescents and adults against meningococcal disease at least 5 years post-vaccination.

Trial registration: ClinicalTrials.gov NCT00356369.

Figures

Fig. 1
Fig. 1
Flow of participants. ACWY-TT = group of participants who received one dose of MenACWY-TT at Month 0; Men-PS = group of participants who received one dose of MenACWY-PS at Month 0; N = number of participants; ATP = according to protocol. *Due to a delay in the annual approval from the FDA of the Philippines for the Year 5 persistence timepoint, all participants enrolled in the Philippines attended the Year 5 visit outside protocol-defined windows between the primary vaccination and the Year 5 blood sampling and hence were eliminated from the ATP analysis at Year 5 because of non-compliance with the blood sampling schedule

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