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
Vaccine and Immunisation Research Group, Peter Doherty Institute at the University of Melbourne, and Murdoch Children's Research Institute, Melbourne, Victoria, Australia.
GSK, Amsterdam, The Netherlands.
Open Forum Infect Dis. 2024 Oct 30;11(11):ofae638. doi: 10.1093/ofid/ofae638. eCollection 2024 Nov.
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.
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.
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.
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.
B 群脑膜炎球菌（MenB）菌株具有高度多样性。通过针对 110 株具有流行病学相关性的 MenB 菌株组成的菌组进行内源性补体-人血清杀菌抗体（enc-hSBA）检测，证明了在 0-2、0-6 或 0-2-6 月龄接种的 MenB 疫苗 4CMenB 的免疫反应广度。
在一项 3 期试验中，3651 名 10 至 25 岁的健康参与者按 5:5:9:1 随机分组，分别接受 4CMenB（0-6 接种程序）、4CMenB（0-2-6 接种程序）、研究性 MenABCWY 疫苗或对照 MenACWY-CRM 疫苗。主要目标是评估安全性，并通过 enc-hSBA 检测，采用基于检测（4CMenB 接种后与对照疫苗接种后对菌株无杀菌活性的样本百分比）和基于应答者（接种后血清能杀灭≥70%菌株的参与者百分比）的方法，针对 MenB 菌株菌组证明免疫反应广度。成功的标准是双侧 97.5%置信区间（CI）下限>65%。通过针对四种指示菌株的传统 hSBA 检测评估免疫原性。
免疫反应广度（基于检测）在 0-2、0-6 和 0-2-6 接种程序中分别为 78.7%（97.5%CI，77.2-80.1）、81.8%（80.4-83.1）、83.2%（81.9-84.4），（基于应答者）分别为 84.8%（81.8-87.5）、89.8%（87.2-92.0）和 93.4%（91.2-95.2）。各接种程序在免疫原性方面未观察到临床相关差异。4CMenB 耐受性良好。
2 剂（0-2、0-6）4CMenB 接种程序在针对多种 MenB 菌株菌组的免疫反应广度终点方面均达到了预先定义的成功标准，具有相当的免疫原性，且安全性与既定的 4CMenB 安全性特征相符。3 剂接种程序未提供额外的免疫学益处，支持使用 4CMenB 0-2 接种程序。
