Beeslaar Johannes, Absalon Judith, Anderson Annaliesa S, Eiden Joseph J, Balmer Paul, Harris Shannon L, Jones Thomas R, O'Neill Robert E, Pregaldien Jean-Louis, Radley David, Maansson Roger, Ginis John, Srivastava Amit, Perez John L
Vaccine Clinical Research and Development, Pfizer Ltd UK, Hurley, UK.
Vaccine Clinical Research and Development, Pfizer Inc, Pearl River, NY, USA.
Infect Dis Ther. 2020 Sep;9(3):641-656. doi: 10.1007/s40121-020-00319-0. Epub 2020 Jul 22.
Two phase 3 studies in adolescents and young adults demonstrated that MenB-FHbp, a meningococcal serogroup B (MenB) vaccine, elicits protective immune responses after 2 or 3 doses based on serum bactericidal antibody assays using human complement (hSBA) against 4 primary and 10 additional diverse, vaccine-heterologous MenB test strains. Lower limits of quantitation (LLOQs; titers 1:8 or 1:16; titers ≥ 1:4 correlate with protection) were used to evaluate responses to individual strains and all 4 primary strains combined (composite response). A post hoc analysis evaluated percentages of subjects with protective responses to as many as 8 strains combined (4 primary plus additional strains).
Immune responses were measured using hSBAs against 4 primary strains in adolescents (n = 1509, MenB-FHbp; n = 898, hepatitis A virus vaccine/saline) and young adults (n = 2480, MenB-FHbp; n = 824, saline) receiving MenB-FHbp or control at 0, 2, and 6 months. Ten additional strains were evaluated in subsets of subjects from approximately 1800 MenB-FHbp recipients across both studies. Percentages of subjects with hSBA titers ≥ LLOQ for different numbers of primary strains or primary plus additional strains combined (7 or 8 strains total per subset) were determined before vaccination, 1 month post-dose 2, and 1 month post-dose 3.
Across the panel of primary plus additional strains, at 1 month post-dose 3, titers ≥ LLOQ were elicited in 93.7-95.7% of adolescents and 91.7-95.0% of young adults for ≥ 5 test strains combined and in 70.5-85.8% of adolescents and 67.5-81.4% of young adults for ≥ 7 strains combined. Among adolescents, 99.8%, 99.0%, 92.8%, and 82.7% had titers ≥ LLOQ against at least 1, 2, 3, and all 4 primary strains, respectively; corresponding percentages for young adults were 99.7%, 97.7%, 94.0%, and 84.5%.
Results support the ability of MenB-FHbp to provide broad coverage against MenB strains expressing diverse FHbp variants.
ClinicalTrials.gov identifiers NCT01830855, NCT01352845.
两项针对青少年和青年的3期研究表明，B群脑膜炎球菌（MenB）疫苗MenB-FHbp，在接种2或3剂后，基于使用人补体的血清杀菌抗体检测（hSBA），可针对4种主要及另外10种不同的、疫苗异源的MenB测试菌株引发保护性免疫反应。定量下限（LLOQ；效价1:8或1:16；效价≥1:4与保护相关）用于评估对各个菌株以及所有4种主要菌株组合（综合反应）的反应。一项事后分析评估了对多达8种菌株组合（4种主要菌株加其他菌株）有保护性反应的受试者百分比。
在0、2和6个月接受MenB-FHbp或对照的青少年（n = 1509，MenB-FHbp；n = 898，甲型肝炎病毒疫苗/生理盐水）和青年（n = 2480，MenB-FHbp；n = 824，生理盐水）中，使用hSBA检测针对4种主要菌株的免疫反应。在两项研究中约1800名MenB-FHbp接种者的受试者亚组中评估另外10种菌株。在接种前、第2剂后1个月和第3剂后1个月，确定针对不同数量的主要菌株或主要菌株加其他菌株组合（每个亚组总共7或8种菌株）且hSBA效价≥LLOQ的受试者百分比。
在主要菌株加其他菌株组中，第3剂后1个月，对于≥5种测试菌株组合，93.7% - 95.7%的青少年和91.7% - 95.0%的青年引发了效价≥LLOQ的反应；对于≥7种菌株组合，则分别为70.5% - 85.8%的青少年和67.5% - 81.4%的青年。在青少年中，分别有99.8%、99.0%、92.8%和82.7%的人针对至少1、2、3和所有4种主要菌株的效价≥LLOQ；青年的相应百分比分别为99.7%、97.7%、94.0%和84.5%。
结果支持MenB-FHbp对表达不同FHbp变体的MenB菌株提供广泛保护的能力。
ClinicalTrials.gov标识符NCT01830855、NCT01352845。
