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Randomized Controlled Trial
. 2022 Dec 31;18(1):1981085.
doi: 10.1080/21645515.2021.1981085. Epub 2021 Oct 6.

Immunological non-inferiority of a new fully liquid presentation of the MenACWY-CRM vaccine to the licensed vaccine: results from a randomized, controlled, observer-blind study in adolescents and young adults

Javier Díez-Domingo  1 , Juan Carlos Tinoco  2 , Airi Poder  3 , Ener Cagri Dinleyici  4 , Haylene Nell  5 , Ignacio Salamanca de la Cueva  6 , Tolga Ince  7 , Edson Duarte Moreira Jr  8 , Khatija Ahmed  9 , Kleber Luz  10 , Yulia Kovshirina  11 , Carlos Eduardo Medina Pech  12 , Tauseefullah Akhund  13 , Valerio Romolini  14 , Marco Costantini  14 , Thembile Mzolo  15 , Barry Kunnel  16 , Isabelle Lechevin  17 , Marianna Aggravi  18 , Paola Tiberi  19 , K Narendran  20 , Juan-Antonio García-Martínez  21 , Venere Basile  22 , Elena Fragapane  13 , Maria Lattanzi  13 , Michele Pellegrini  13
Affiliations
Randomized Controlled Trial

Immunological non-inferiority of a new fully liquid presentation of the MenACWY-CRM vaccine to the licensed vaccine: results from a randomized, controlled, observer-blind study in adolescents and young adults

Javier Díez-Domingo et al. Hum Vaccin Immunother. .

Abstract

A fully liquid MenACWY-CRM vaccine presentation has been developed, modifying the meningococcal serogroup A (MenA) component from lyophilized to liquid. The safety and immunogenicity of the liquid presentation at the end of the intended shelf-life (aged for 24 or 30 months) were compared to the licensed lyophilized/liquid presentation. This multicenter, randomized (1:1), observer-blind, phase 2b study (NCT03433482) enrolled adolescents and young adults (age 10-40 years). In part 1, 844 participants received one dose of liquid presentation stored for approximately 24 months or licensed presentation. In part 2, 846 participants received one dose of liquid presentation stored for approximately 30 months or licensed presentation. After storage, the MenA free saccharide (FS) level was approximately 25% and O-acetylation was approximately 45%. The primary objective was to demonstrate non-inferiority of the liquid presentation to licensed presentation, as measured by human serum bactericidal assay (hSBA) geometric mean titers (GMTs) against MenA, 1-month post-vaccination. Immune responses against each vaccine serogroup were similar between groups. Between-group ratios of hSBA GMTs for MenA were 1.21 (part 1) and 1.11 (part 2), with two-sided 95% confidence interval lower limits (0.94 and 0.87, respectively) greater than the prespecified non-inferiority margin (0.5), thus meeting the primary study objective. No safety concerns were identified. Despite reduced O-acetylation of MenA and increased FS content, serogroup-specific immune responses induced by the fully liquid presentation were similar to those induced by the licensed MenACWY-CRM vaccine, with non-inferior anti-MenA responses. The safety profiles of the vaccine presentations were similar.

Keywords: MenACWY-CRM; adolescents; human serum bactericidal assay; meningococcal serogroup A; non-inferiority.

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Conflict of interest statement

T.A., V.R., M.C., T.M., B.K., I.L., M.L., E.F., V.B., M.A., J.-A.G.-M., P.T., K.N., and M.P. are employed by the GSK group of companies. T.A., M.L., E.F., V.B., M.A., and M.P. hold shares in the GSK group of companies. J.D.-D. reports payments from the GSK group of companies and Sanofi Pasteur to his institution, outside the submitted work. E.C.D. reports payments from the GSK group of companies to his institution for the conduct of the study, and Sanofi Pasteur and Pfizer, outside the submitted work. I.S.C. reports payments from the GSK group of companies, Sanofi Pasteur, MSD, and Pfizer, outside the submitted work. E.D.M. Jr reports payments from the GSK group of companies to his institution for the conduct of the study. J.D.-D., E.C.D., I.S.C., E.D.M. Jr, T.A., V.R., M.C., T.M., B.K., I.L., M.L., E.F., V.B., M.A., J.-A.G.-M., P.T., K.N., and M.P. declare no other financial and non-financial relationships and activities. J.C.T., A.P., H.N., I.S.C., T.I., K.A., K.L., Y.K. and C.E.M.P. declare no financial and non-financial relationships and activities and no conflicts of interest.

Figures

Figure 1.
Figure 1.
Study highlights.
Figure 2.
Figure 2.
Trial profile and demographic characteristics of vaccinated study participants. PPI, per-protocol population for immunogenicity.
Figure 3.
Figure 3.
Percentages of participants (with 95% confidence intervals) with (a,b) human serum bactericidal assay (hSBA) titer ≥8 at 1-month post-vaccination and (c,d) four-fold increase in hSBA titer from baseline to 1-month post-vaccination against serogroups A, C, W, and Y (per-protocol population for immunogenicity).
Figure 4.
Figure 4.
Percentages of participants reporting solicited local and systemic adverse events within 7 days of vaccination (solicited safety population).
Figure 5.
Figure 5.
Number (percentage) of participants reporting unsolicited adverse events (AEs) during the 1-month and 6-month post-vaccination periods (unsolicited safety population).
See this image and copyright information in PMC

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