4CMenB Breadth of Immune Response, Immunogenicity, and Safety: Results From a Phase 3 Randomized, Controlled, Observer Blind Study in Adolescents and Young Adults

Terry Nolan; Chiranjiwi Bhusal; Jiří Beran; Mark Bloch; Benhur S Cetin; Ener C Dinleyici; Daniel Dražan; Satu Kokko; Susanna Koski; Outi Laajalahti; Joanne M Langley; Mika Rämet; Peter C Richmond; Peter Silas; Bruce Tapiero; Florence Tiong; Mary Tipton; Benita Ukkonen; Betul Ulukol; Maria Lattanzi; Mauro Trapani; Arnold Willemsen; Daniela Toneatto; QUINTET study group

doi:10.1093/ofid/ofae638

4CMenB Breadth of Immune Response, Immunogenicity, and Safety: Results From a Phase 3 Randomized, Controlled, Observer Blind Study in Adolescents and Young Adults

Open Forum Infect Dis. 2024 Oct 30;11(11):ofae638. doi: 10.1093/ofid/ofae638. eCollection 2024 Nov.

Authors

Terry Nolan¹, Chiranjiwi Bhusal², Jiří Beran³, Mark Bloch^{4

5}, Benhur S Cetin⁶, Ener C Dinleyici⁷, Daniel Dražan⁸, Satu Kokko⁹, Susanna Koski¹⁰, Outi Laajalahti¹¹, Joanne M Langley¹², Mika Rämet¹³, Peter C Richmond¹⁴, Peter Silas¹⁵, Bruce Tapiero^{16

17}, Florence Tiong¹⁸, Mary Tipton¹⁹, Benita Ukkonen²⁰, Betul Ulukol²¹, Maria Lattanzi²², Mauro Trapani²², Arnold Willemsen², Daniela Toneatto²²; QUINTET study group

Collaborators

QUINTET study group:
Ronald Ackerman, Renata Adamovska, Eugene Athan, Kwabena Ayesu, Jiří Beran, David Bernard, Chiranjiwi Bhusal, Mark Bloch, William Byars, Robert Carter, Benhur Cetin, Maia Chakerian, Marije Dalebout, Ferdinandus de Looze, Ener Cagri Dinleyici, Marc Dionne, Daniel Dražan, Peter Dzongowski, Rand Farjo, Daniel Finn, George Freeman, Ryan Gottfredson, Paul Grubb, Anil Gupta, Tolga Ince, Robert Jeanfreau, Jake Jones, James Kellner, Kaia Kiiroja, Satu Kokko, Susanna Koski, Joanne Langley, Outi Laajalahti, Maria Lattanzi, Isabelle Lechevin, Hemalini Mehta, Sandra Meisalu, Danielle Morelle, Terry Nolan, Alexander Osowa, Pauliina Paavola, Minesh Patel, Miroslav Pavlasek, Enrique Pelayo, Mika Rämet, Stefanie Raulier, Peter Richmond, Walter Rok, Rambod Rouhbakhsh, Manish Sadarangani, Yamirka Sanchez, Martin Schear, John Scott, Ilkka Seppä, Peter Silas, William Simon, Martina Spaziererova, Jonathan Staben, Joseph Surber, Bruce Tapiero, Florence Tiong, Mary Tipton, Daniela Toneatto, Mauro Trapani, Benita Ukkonen, Betul Ulukol, Marie-Louise Vachon, Noah Vale, Dominique Wauters, Arnold Willemsen, Josef Zemanek

Affiliations

¹ Vaccine and Immunisation Research Group, Peter Doherty Institute at the University of Melbourne, and Murdoch Children's Research Institute, Melbourne, Victoria, Australia.
² GSK, Amsterdam, The Netherlands.
³ Vaccination and Travel Medicine Centre, Hradec Králové, Czechia.
⁴ Holdsworth House Medical Practice, Sydney, NSW, Australia.
⁵ Department of Medicine, Kirby Institute, University of New South Wales, Sydney, NSW, Australia.
⁶ Department of Pediatric Infectious Diseases, Erciyes University Faculty of Medicine, Kayseri, Türkiye.
⁷ Eskisehir Osmangazi University Faculty of Medicine, Eskisehir, Türkiye.
⁸ General Practice for Children and Adolescents, Jindřichův Hradec, Czechia.
⁹ Oulu Vaccine Research Clinic, FVR Finnish Vaccine Research and Tampere University, Oulu, Finland.
¹⁰ Helsinki South Clinic, FVR Finnish Vaccine Research and Tampere University, Finland.
¹¹ FVR Finnish Vaccine Research and Tampere University, Seinäjoen Rokotetutkimusklinikka, Seinäjoki, Finland.
¹² Canadian Center for Vaccinology (Dalhousie University, IWK Health and Nova Scotia Health), Halifax, NS, Canada.
¹³ Faculty of Medicine and Health Technology, FVR Finnish Vaccine Research, Tampere University, Tampere, Finland.
¹⁴ University of Western Australia School of Medicine and Vaccine Trials Group, Telethon Kids Institute, Nedlands, Washington, Australia.
¹⁵ Wee Care Pediatrics, Syracuse, Utah, USA.
¹⁶ CHU Sainte-Justine, Montreal, QC, Canada.
¹⁷ Infectious Diseases Division, Department of Pediatrics, University of Montreal, QC, Canada.
¹⁸ AusTrials (Wellers Hill), Tarragindi, QLD, Australia.
¹⁹ Copperview Medical Center, South Jordan, Utah, USA.
²⁰ FVR Finnish Vaccine Research and Tampere University, Espoo Clinic, Espoo, Finland.
²¹ Department of Pediatrics, Ankara University School of Medicine, Ankara, Türkiye.
²² GSK, Siena, Italy.

Abstract

Background: Meningococcal serogroup B (MenB) strains are highly diverse. Breadth of immune response for the MenB vaccine, 4CMenB, administered at 0-2, 0-6, or 0-2-6 months, was demonstrated by endogenous complement-human serum bactericidal antibody (enc-hSBA) assay against an epidemiologically relevant panel of 110 MenB strains.

Methods: In a phase 3 trial, 3651 healthy 10- to 25-year-old participants were randomized 5:5:9:1 to receive 4CMenB (0-6 schedule), 4CMenB (0-2-6 schedule), investigational MenABCWY vaccine, or control MenACWY-CRM vaccine. The primary objectives were to evaluate safety and demonstrate breadth of immune response by enc-hSBA assay against the MenB strain panel using test-based (percentage of samples without bactericidal activity against strains after 4CMenB vs control vaccination) and responder-based (percentage of participants whose postvaccination sera kill ≥70% strains) approaches. Success was demonstrated with 2-sided 97.5% confidence interval (CI) lower limit >65%. Immunogenicity was assessed by traditional hSBA assay against four indicator strains.

Results: Breadth of immune response (test-based) was 78.7% (97.5% CI, 77.2-80.1), 81.8% (80.4-83.1), 83.2% (81.9-84.4) for the 0-2, 0-6, and 0-2-6 schedules, respectively, and (responder-based) 84.8% (81.8-87.5), 89.8% (87.2-92.0), and 93.4% (91.2-95.2), respectively. No clinically relevant differences in immunogenicity were observed across schedules. 4CMenB was well tolerated.

Conclusions: The 2-dose (0-2, 0-6) 4CMenB schedules met predefined criteria for success for both breadth of immune response endpoints against a diverse MenB strain panel, had comparable immunogenicity, and safety in line with the established 4CMenB safety profile. The 3-dose schedule provided no additional immunological benefit, supporting use of the 4CMenB 0-2 schedule.

Keywords: 4CMenB; Neisseria meningitidis; bactericidal assay; breadth of immune response; meningococcal vaccine.

Publication types

Clinical Trial