4CMenB Breadth of Immune Response, Immunogenicity, and Safety: Results From a Phase 3 Randomized, Controlled, Observer Blind Study in Adolescents and Young Adults
Authors: Nolan Terry , Bhusal Chiranjiwi , Beran Jiří , Bloch Mark , Cetin Benhur S , Dinleyici Ener C , Dražan Daniel , Kokko Satu , Koski Susanna , Laajalahti Outi , Langley Joanne M , Rämet Mika , Richmond Peter C , Silas Peter , Tapiero Bruce , Tiong Florence , Tipton Mary , Ukkonen Benita , Ulukol Betul , Lattanzi Maria , Trapani Mauro , Willemsen Arnold , Toneatto Daniela ,   the QUINTET study group, Ackerman Ronald , Adamovska Renata , Athan Eugene , Ayesu Kwabena , Beran Jiří , Bernard David , Bhusal Chiranjiwi , Bloch Mark , Byars William , Carter Robert , Cetin Benhur , Chakerian Maia , Dalebout Marije , de Looze Ferdinandus , Dinleyici Ener Cagri , Dionne Marc , Dražan Daniel , Dzongowski Peter , Farjo Rand , Finn Daniel , Freeman George , Gottfredson Ryan , Grubb Paul , Gupta Anil , Ince Tolga , Jeanfreau Robert , Jones Jake , Kellner James , Kiiroja Kaia , Kokko Satu , Koski Susanna , Langley Joanne , Laajalahti Outi , Lattanzi Maria , Lechevin Isabelle , Mehta Hemalini , Meisalu Sandra , Morelle Danielle , Nolan Terry , Osowa Alexander , Paavola Pauliina , Patel Minesh , Pavlasek Miroslav , Pelayo Enrique , Rämet Mika , Raulier Stefanie , Richmond Peter , Rok Walter , Rouhbakhsh Rambod , Sadarangani Manish , Sanchez Yamirka , Schear Martin , Scott John , Seppä Ilkka , Silas Peter , Simon William , Spaziererova Martina , Staben Jonathan , Surber Joseph , Tapiero Bruce , Tiong Florence , Tipton Mary , Toneatto Daniela , Trapani Mauro , Ukkonen Benita , Ulukol Betul , Vachon Marie-Louise , Vale Noah , Wauters Dominique , Willemsen Arnold , Zemanek Josef 
Published: October 2024

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 &gt;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.