TY - JOUR
T1 - A new fully liquid presentation of MenACWY-CRM conjugate vaccine: Results from a multicentre, randomised, controlled, observer-blind study
AU - Vandermeulen, Corinne
AU - Leroux-Roels, Isabel
AU - Vandeleur, James
AU - Staniscia, Tommaso
AU - Girard, Ginette
AU - Ferguson, Murdo
AU - Icardi, Giancarlo
AU - Schwarz, Tino F.
AU - Neville, A. Munro
AU - Nolan, Terry
AU - Cinquetti, Sandro
AU - Akhund, Tauseefullah
AU - Van Huyneghem, Sofie
AU - Aggravi, Marianna
AU - Kunnel, Barry
AU - de Wergifosse, Bertrand
AU - Domenico, Gabriele Filippo Di
AU - Costantini, Marco
AU - Vir Singh, Puneet
AU - Fragapane, Elena
AU - Lattanzi, Maria
AU - Pellegrini, Michele
N1 - Funding Information:
The authors thank all participants, the clinical teams, the investigators involved in this study and the CCP team, especially Naresh Aggarwal, Wayne Ghesquiere, Axel Schaefer, Peter Dzongowski, Angela Molga, Keith Potent, Jeannette Comeau, Naveen Garg and Jo Van Effen. The authors thank the GSK teams for their contributions to the study, especially Cristel Stalens, Pavitra Keshavan, Silvia Barbi, Frans Corthals, Thembile Mzolo, Massimo Bianchini, Isabelle Lechevin, Francesco Berti, Venere Basile, Malte Meppen, Valerio Romolini, Nicholas Martin, Beno?t Thumas and Valeria Gina Clausi. The authors also thank Business & Decision Life Sciences platform for editorial assistance and manuscript coordination, on behalf of GSK. Joanne Knowles (independent medical writer, on behalf of Business & Decision Life Sciences) provided medical writing support. Bruno Dumont (Business & Decision Life Sciences, on behalf of GSK) coordinated the manuscript development and editorial support. TA, MA, EF, ML and MP were involved in the study conception and design. CV, ILR, JV, TS, GG, MF, GI, TFS, AMN, TN, SC, TA, SVH, BK, BdW and MP were involved in acquisition and generation of data and/or performed the study. CV, TA, GFDD, MC, PVS, ML and MP were involved in data analysis and data interpretation. All authors contributed substantially to the development of the manuscript and approved the final version. All authors attest they meet the ICMJE criteria for authorship. This study was funded by GlaxoSmithKline Biologicals SA, which was involved in all stages of study conduct, including analysis of the data. GlaxoSmithKline Biologicals SA also took in charge all costs associated with the development and publication of this manuscript. Menveo is a trademark owned by or licensed to the GSK group of companies. Anonymised individual participant data and study documents can be requested for further research fromwww.clinicalstudydatarequest.com.
Publisher Copyright:
© 2021 GlaxoSmithKline Biologicals S.A.
PY - 2021
Y1 - 2021
N2 - Background: The currently licensed quadrivalent MenACWY-CRM conjugate vaccine presentation consists of two vials (lyophilised MenA and liquid MenCWY) to be reconstituted before injection. A new fully liquid formulation in a single vial has been developed to further improve the vaccine presentation. Since the MenA structure is subject to hydrolytic degradation, this study was conducted to compare the immunogenicity and safety of the investigational MenACWY-CRM liquid vaccine with the licensed vaccine. Methods: In this multicentre, randomised, controlled, observer-blind, phase 2b study, 979 healthy adults were administered a single dose of MenACWY-CRM liquid presentation or the currently licensed MenACWY-CRM vaccine. MenA free saccharide generation was accelerated to approximately 30% in the liquid presentation and MenA polysaccharide O-acetylation was reduced to approximately 40%, according to a controlled procedure. Immunological non-inferiority of the MenACWY-CRM liquid to the licensed vaccine, as measured by human serum bactericidal assay (hSBA) geometric mean titres (GMTs) against MenA 1 month post-vaccination, was the primary study objective. Safety assessment was among the secondary objectives. Results: Immune responses against each serogroup were similar between the two vaccine groups and was non-inferior for MenA. Adjusted hSBA GMTs for MenA were 185.16 and 211.33 for the MenACWY-CRM liquid presentation and currently licensed vaccine presentation, respectively. The between-group ratio of hSBA GMTs for MenA was 0.88, with a two-sided 95% confidence interval lower limit of 0.64, greater than the prespecified non-inferiority margin of 0.5, thus meeting the primary study objective. Both vaccines were well tolerated. No serious adverse events were considered related to vaccination. Conclusions: The levels of MenA free saccharide and polysaccharide O-acetylation did not affect the immunogenicity of the fully liquid presentation, which was demonstrated to be non-inferior to the immunogenicity of the currently licensed MenACWY-CRM vaccine against MenA. The immunogenicity, reactogenicity and safety profiles of the two vaccine presentations were similar.
AB - Background: The currently licensed quadrivalent MenACWY-CRM conjugate vaccine presentation consists of two vials (lyophilised MenA and liquid MenCWY) to be reconstituted before injection. A new fully liquid formulation in a single vial has been developed to further improve the vaccine presentation. Since the MenA structure is subject to hydrolytic degradation, this study was conducted to compare the immunogenicity and safety of the investigational MenACWY-CRM liquid vaccine with the licensed vaccine. Methods: In this multicentre, randomised, controlled, observer-blind, phase 2b study, 979 healthy adults were administered a single dose of MenACWY-CRM liquid presentation or the currently licensed MenACWY-CRM vaccine. MenA free saccharide generation was accelerated to approximately 30% in the liquid presentation and MenA polysaccharide O-acetylation was reduced to approximately 40%, according to a controlled procedure. Immunological non-inferiority of the MenACWY-CRM liquid to the licensed vaccine, as measured by human serum bactericidal assay (hSBA) geometric mean titres (GMTs) against MenA 1 month post-vaccination, was the primary study objective. Safety assessment was among the secondary objectives. Results: Immune responses against each serogroup were similar between the two vaccine groups and was non-inferior for MenA. Adjusted hSBA GMTs for MenA were 185.16 and 211.33 for the MenACWY-CRM liquid presentation and currently licensed vaccine presentation, respectively. The between-group ratio of hSBA GMTs for MenA was 0.88, with a two-sided 95% confidence interval lower limit of 0.64, greater than the prespecified non-inferiority margin of 0.5, thus meeting the primary study objective. Both vaccines were well tolerated. No serious adverse events were considered related to vaccination. Conclusions: The levels of MenA free saccharide and polysaccharide O-acetylation did not affect the immunogenicity of the fully liquid presentation, which was demonstrated to be non-inferior to the immunogenicity of the currently licensed MenACWY-CRM vaccine against MenA. The immunogenicity, reactogenicity and safety profiles of the two vaccine presentations were similar.
KW - Conjugate vaccine
KW - Immune response
KW - MenA free saccharide
KW - MenACWY
KW - Neisseria meningitidis
KW - O-acetylation
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U2 - 10.1016/j.vaccine.2021.09.068
DO - 10.1016/j.vaccine.2021.09.068
M3 - Article
AN - SCOPUS:85116837387
JO - Vaccine
JF - Vaccine
SN - 0264-410X
ER -