A phase 2b/3b MenACWY-TT study of long-term antibody persistence after primary vaccination and immunogenicity and safety of a booster dose in individuals aged 11 through 55 years

Charissa Fay Corazon Borja-Tabora, Paula Peyrani, Chris Webber, Marie Van der Wielen, Brigitte Cheuvart, Nathalie De Schrevel, Veronique Bianco, Emmanuel Aris, Mark Cutler, Ping Li, John L Perez, Charissa Fay Corazon Borja-Tabora, Paula Peyrani, Chris Webber, Marie Van der Wielen, Brigitte Cheuvart, Nathalie De Schrevel, Veronique Bianco, Emmanuel Aris, Mark Cutler, Ping Li, John L Perez

Abstract

Background: A previous phase 2 study demonstrated the immunogenicity of a single dose of meningococcal A, C, W, Y-tetanus toxoid conjugate (MenACWY-TT) or polysaccharide (MenACWY-PS) vaccine for up to 5 years in individuals aged 11-55 years. This follow-up study evaluated long-term antibody persistence up to 10 years and the immunogenicity and safety of a single MenACWY-TT booster dose given 10 years after primary vaccination.

Methods: Blood draws were conducted annually in Years 7-10. At Year 10, all subjects received a MenACWY-TT booster dose. Blood was drawn at 1 month and safety data were collected ≤6 months postbooster. Study endpoints included immunogenicity during the persistence phase (primary), and immunogenicity and safety during the booster phase (secondary). Statistical analyses were descriptive.

Results: A total of 311 subjects were enrolled in the persistence phase (MenACWY-TT, 235; MenACWY-PS, 76); 220 were enrolled in the booster phase (MenACWY-TT, 164; MenACWY-PS, 56). Descriptive analyses indicated that at Years 7-10, the percentages of subjects achieving serum bactericidal antibody assay using baby rabbit complement (rSBA) titers ≥1:8 and ≥1:128 were higher for serogroups A, W, and Y in the MenACWY-TT versus MenACWY-PS group; percentages were similar across groups for serogroup C. rSBA geometric mean titers (GMTs) for serogroups A, W, and Y were higher in the MenACWY-TT group and slightly higher in the MenACWY-PS group for serogroup C. One month postbooster, all primary MenACWY-TT and ≥98.1% of primary MenACWY-PS recipients had rSBA titers ≥1:8. For all serogroups, rSBA GMTs postbooster were higher in the MenACWY-TT versus MenACWY-PS group. Most local and general reactogenicity events were similar between groups and mild to moderate in severity. Adverse events at 1 month postbooster were 9.1% for the MenACWY-TT and 3.6% for the MenACWY-PS groups; all were nonserious.

Conclusions: Immune responses to a single MenACWY-TT primary dose administered at age 11-55 years persisted in >70% of individuals evaluated at Years 7-10. A MenACWY-TT booster dose administered at Year 10 was safe and immunogenic with no new safety signals observed. These results provide important insights regarding long-term protection from primary vaccination and the benefits of booster dosing.

Trial registration: Clinicaltrials.gov, NCT01934140. Registered September 2013.

Keywords: Antibody; Booster; Immunogenicity; MenACWY-TT; Meningococcal; Persistence; Vaccine.

Conflict of interest statement

CB-T’s institution received grants from the GSK group of companies. PP, CW, MC, PL, and JP are employees of Pfizer. MVW, BC, NS, EA, and VB are employees of GlaxoSmithKline.

Figures

Fig. 1
Fig. 1
Study design. Randomization, the primary vaccination phase, the initial antibody persistence phase (Years 1–5), the current long-term persistence phase (Years 7–10)*, and the booster dosing phase are shown. MenACWY meningococcal A, C, W, Y, PS polysaccharide, TT tetanus toxoid *Study visits for Year 6 of the persistence phase were not conducted due to delay in study approval
Fig. 2
Fig. 2
Subject disposition in the antibody persistence phase* and the booster phase.MenACWY meningococcal A, C, W, Y, PS polysaccharide, TT tetanus toxoid *Years 7–10 after the primary vaccination †Completed all visits, n = 203
Fig. 3
Fig. 3
Subjects* with rSBA titers ≥1:8 at 7–10 years after the primary vaccination with MenACWY-TT or MenACWY-PS MenACWY meningococcal A, C, W, Y, PS polysaccharide, rSBA serum bactericidal antibody assay using baby rabbit complement, TT tetanus toxoid *In the according-to-protocol cohort for persistence
Fig. 4
Fig. 4
Subjects* reporting reactogenicity events within 4 days of receiving the MenACWY-TT booster. Both local and general reactogenicity events by intensity and the primary vaccine group are shown. Intensity scales are summarized in Additional File 1: Table S1. GI gastrointestinal, MenACWY meningococcal A, C, W, Y, PS polysaccharide, TT tetanus toxoid *In the booster total vaccinated cohort for safety

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