MenB-FHbp疫苗被许可用于预防2剂量(0、6个月)或3剂量(0、1-2、6个月)系列的脑膜炎球菌血清群B疾病。该3期研究进一步评估了2剂量MenB-FHbp方案的免疫原性和安全性。
10-25岁的受试者接受MenB-FHbp(0、6个月)和四价脑膜炎球菌结合疫苗MenACWY-CRM(0个月)。主要免疫原性终点包括使用4种不同的人补体(hSBA)滴度的血清杀菌抗体从基线增加≥4倍的受试者百分比,疫苗-异源主要血清群B测试菌株和滴度≥定量下限(LLOQ;1:8或1:16)对于剂量2后的所有4个主要菌株组合(复合应答);滴度≥1:4是公认的保护相关性。还评估了10种其他疫苗异源菌株的hSBA滴度≥LLOQ的参与者的百分比;确定了初级菌株响应对次级菌株响应的阳性预测值。安全性进行了评估。
总的来说,1057名受试者接受剂量1,946名受试者接受剂量2的MenB-FHbp。在剂量2后,针对每种主要菌株的hSBA滴度增加≥4倍的参与者的百分比范围为67.4%至95.0%,复合反应为74.3%。初级应变响应高度预测次级应变响应。大多数反应原性事件的严重程度为轻度至中度,并未导致退出研究。研究者认为与疫苗接种有关的不良事件(AE)发生在4.2%(44/1057)的受试者中,并且没有严重的AE或新诊断的慢性疾病被认为与疫苗接种有关。
在0、6个月时施用的MenB-FHbp具有良好的耐受性,并且诱导针对不同血清群B菌株的保护性杀菌抗体应答。研究结果为在该人群中以2剂量方案继续使用MenB-FHbp提供了进一步的支持。
The MenB-FHbp vaccine is licensed to prevent meningococcal serogroup B disease on either a 2-dose (0, 6 months) or 3-dose (0, 1-2, 6 months) series. This phase 3
study further assessed the immunogenicity and safety of the 2-dose MenB-FHbp schedule.
Subjects 10-25 years of age received MenB-FHbp (months 0, 6) and the quadrivalent meningococcal conjugate vaccine MenACWY-CRM (month 0). Primary immunogenicity endpoints included percentages of subjects achieving ≥ 4-fold increases from baseline in serum bactericidal antibody using human complement (hSBA) titers for 4 diverse, vaccine-heterologous primary serogroup B test strains and titers ≥ lower limit of quantitation (LLOQ; 1:8 or 1:16) for all 4 primary strains combined (composite response) after dose 2; a titer ≥ 1:4 is the accepted correlate of protection. Percentages of participants with hSBA titers ≥ LLOQ for 10 additional vaccine-heterologous strains were also assessed; positive predictive values of primary strain responses for secondary strain responses were determined. Safety was assessed.
Overall, 1057 subjects received dose 1 and 946 received dose 2 of MenB-FHbp. Percentages of participants achieving ≥ 4-fold increases in hSBA titers against each primary strain after dose 2 ranged from 67.4% to 95.0% and the composite response was 74.3%. Primary strain responses were highly predictive of secondary strain responses. Most reactogenicity events were mild-to-moderate in severity and did not lead to withdrawal from the
study. Adverse events (AEs) considered by the investigator to be related to vaccination occurred in 4.2% (44/1057) of subjects, and there were no serious AEs or newly diagnosed chronic medical conditions considered related to vaccination.
MenB-FHbp administered at 0, 6 months was well tolerated and induced protective bactericidal antibody responses against diverse serogroup B strains. Findings provide further support for the continued use of MenB-FHbp on a 2-dose schedule in this population.