A new fully liquid presentation of MenACWY-CRM conjugate vaccine: Results from a multicentre, randomised, controlled, observer-blind study

Corinne Vandermeulen; Isabel Leroux-Roels; James Vandeleur; Tommaso Staniscia; Ginette Girard; Murdo Ferguson; Giancarlo Icardi; Tino F Schwarz; A Munro Neville; Terry Nolan; Sandro Cinquetti; Tauseefullah Akhund; Sofie Van Huyneghem; Marianna Aggravi; Barry Kunnel; Bertrand de Wergifosse; Gabriele Filippo Di Domenico; Marco Costantini; Puneet Vir Singh; Elena Fragapane; Maria Lattanzi; Michele Pellegrini

doi:10.1016/j.vaccine.2021.09.068

A new fully liquid presentation of MenACWY-CRM conjugate vaccine: Results from a multicentre, randomised, controlled, observer-blind study

Vaccine. 2021 Oct 29;39(45):6628-6636. doi: 10.1016/j.vaccine.2021.09.068. Epub 2021 Oct 9.

Authors

Corinne Vandermeulen¹, Isabel Leroux-Roels², James Vandeleur³, Tommaso Staniscia⁴, Ginette Girard⁵, Murdo Ferguson⁶, Giancarlo Icardi⁷, Tino F Schwarz⁸, A Munro Neville⁹, Terry Nolan¹⁰, Sandro Cinquetti¹¹, Tauseefullah Akhund¹², Sofie Van Huyneghem¹³, Marianna Aggravi¹⁴, Barry Kunnel¹⁵, Bertrand de Wergifosse¹⁶, Gabriele Filippo Di Domenico¹⁷, Marco Costantini¹⁸, Puneet Vir Singh¹⁹, Elena Fragapane²⁰, Maria Lattanzi²¹, Michele Pellegrini²²

Affiliations

¹ Leuven University Vaccinology Centre, Department of Public Health and Primary Care, KU Leuven, Kapucijnenvoer 35, PO 7001, 3000 Leuven, Belgium. Electronic address: [email protected].
² Center for Vaccinology, Ghent University and Ghent University Hospital, Ghent, Belgium. Electronic address: [email protected].
³ Paratus Clinical Blacktown Clinic, Main Street, Blacktown, NSW 2148, Australia.
⁴ Department of Medicine and Aging Sciences, 'G. d'Annunzio' University Chieti-Pescara, Via dei Vestini 31, 66100 Chieti, Italy. Electronic address: [email protected].
⁵ Diex Research, 15 J.-A. Bombardier, Sherbrooke, Québec J1L 0H8, Canada. Electronic address: [email protected].
⁶ Colchester Research Group, 68 Robie Street, Truro, Nova Scotia, Canada. Electronic address: [email protected].
⁷ Department of Health Sciences (Dissal), University of Genoa, and Hygiene Unit, IRCCS Policlinico San Martino Hospital, Genoa, Italy. Electronic address: [email protected].
⁸ Klinikum Würzburg Mitte, Standort Juliusspital, Salvatorstr. 7, 97074 Würzburg, Germany. Electronic address: [email protected].
⁹ AusTrials, Level 3, Westside Private Hospital, 32 Morrow St, Taringa, QLD 4068, Australia. Electronic address: [email protected].
¹⁰ Peter Doherty Institute for Infection and Immunity, University of Melbourne, Melbourne, Victoria 3010, Australia; Murdoch Children's Research Institute, Parkville, Victoria 3052, Australia. Electronic address: [email protected].
¹¹ Public Health Department, Local Health Unit N. 2 'Marca Trevigiana', Treviso, Veneto Region, Italy. Electronic address: [email protected].
¹² GSK, Clinical Research and Development Centre, Via Fiorentina 1, Siena 53100, Italy. Electronic address: [email protected].
¹³ GSK, Regional Evidence Generation, Avenue Pascal 2, 4, 6, 1300 Wavre, Belgium. Electronic address: [email protected].
¹⁴ GSK, Technical Development, Via Fiorentina 1, Siena 53100, Italy. Electronic address: [email protected].
¹⁵ GSK, Data Strategy & Management, Global Clinical Operations Development - R&D, Hullenbergweg 83-85, 1101CL Amsterdam, the Netherlands. Electronic address: [email protected].
¹⁶ GSK, Clinical Laboratory Sciences, Rue de l'Institut, 89, 1330 Rixensart, Belgium. Electronic address: [email protected].
¹⁷ GSK, Biostatistics and Statistical Programming, Via Fiorentina 1, Siena 53100, Italy. Electronic address: [email protected].
¹⁸ GSK, Biostatistics and Statistical Programming, Via Fiorentina 1, Siena 53100, Italy. Electronic address: [email protected].
¹⁹ GSK, Safety Evaluation and Risk Management, Via Fiorentina 1, Siena 53100, Italy. Electronic address: [email protected].
²⁰ GSK, Clinical Research and Development Centre, Via Fiorentina 1, Siena 53100, Italy. Electronic address: [email protected].
²¹ GSK, Clinical Research and Development Centre, Via Fiorentina 1, Siena 53100, Italy. Electronic address: [email protected].
²² GSK, Clinical Research and Development Centre, Via Fiorentina 1, Siena 53100, Italy. Electronic address: [email protected].

PMID: 34635373
DOI: 10.1016/j.vaccine.2021.09.068

Abstract

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.

Keywords: Conjugate vaccine; Immune response; MenA free saccharide; MenACWY; Neisseria meningitidis; O-acetylation.

Publication types

Multicenter Study
Randomized Controlled Trial
Research Support, Non-U.S. Gov't

MeSH terms

Adult
Antibodies, Bacterial
Humans
Meningococcal Infections*
Meningococcal Vaccines*
Vaccination
Vaccines, Conjugate

Substances

Antibodies, Bacterial
MenACWY
MenACWY-CRM vaccine
Meningococcal Vaccines
Vaccines, Conjugate