Kaiser Permanente Vaccine Study Center, 1 Kaiser Plaza, 16th Floor, Oakland, CA 94612, United States.
Clinic of Children's Infectious Diseases, Černopolní 212/9, 662 63 Brno, Czech Republic.
Vaccine. 2018 Apr 19;36(17):2356-2363. doi: 10.1016/j.vaccine.2018.02.085. Epub 2018 Mar 22.
Individuals with functional or anatomic asplenia are at high risk for meningococcal disease. We evaluated the immunogenicity and safety of 1 and 2 doses of the quadrivalent meningococcal serogroups A, C, W, Y tetanus toxoid-conjugate vaccine (MenACWY-TT) in this high-risk population.
This phase III, open-label, controlled, non-randomized study (NCT01641042) enrolled 1-17-year-olds with impaired splenic activity (high-risk group) and age-matched healthy controls (control group). We measured immune responses to MenACWY-TT by serum bactericidal activity assays using rabbit (rSBA) and human (hSBA) complement and in terms of antibodies against polysaccharides of the 4 vaccine serogroups. We evaluated vaccine response rates (VRRs) as 4-fold increases from pre-vaccination levels or titers ≥1:32 (rSBA)/≥1:8 (hSBA). We recorded solicited and unsolicited adverse events (AEs) during 4 and 31 days post-vaccination, and serious AEs (SAEs) and new onset of chronic illnesses (NOCIs) throughout the study.
The according-to-protocol cohort for immunogenicity included 40 participants per group. In both groups, the first MenACWY-TT dose induced rSBA VRRs of 92.5-100% and hSBA VRRs of 55.6-77.1% across vaccine serogroups. Following the second MenACWY-TT dose, all participants had high responses, with rSBA and hSBA VRRs of 73.0-100% across vaccine serogroups. rSBA and hSBA geometric mean titers for each serogroup increased in both groups (with different magnitudes, but ≥13.1-fold) compared with baseline levels. Polysaccharide antibody concentrations ≥2.0 μg/ml were detected in ≥84.4% of participants and were similar between groups. Incidences of solicited and unsolicited AEs were comparable between groups. We recorded SAEs in 4/43 participants in the high-risk group and 1/43 participants in the control group (none vaccine-related). No NOCIs were reported.
In this descriptive study, MenACWY-TT induced similar functional and humoral immune responses and had a clinically acceptable safety profile in children and adolescents with impaired splenic activity and in healthy controls.
功能性或解剖性无脾个体患脑膜炎球菌病的风险很高。我们评估了 1 剂和 2 剂四价脑膜炎球菌血清群 A、C、W、Y 破伤风类毒素结合疫苗（MenACWY-TT）在这一高危人群中的免疫原性和安全性。
这是一项 III 期、开放标签、对照、非随机研究（NCT01641042），纳入了脾脏功能受损（高危组）和年龄匹配的健康对照（对照组）的 1-17 岁儿童。我们通过使用兔（rSBA）和人（hSBA）补体的血清杀菌活性测定法以及针对 4 种疫苗血清型多糖的抗体来测量对 MenACWY-TT 的免疫反应。我们将疫苗反应率（VRR）定义为与接种前水平相比增加 4 倍或滴度≥1：32（rSBA）/≥1：8（hSBA）。我们记录了接种后 4 天和 31 天的疫苗相关和非疫苗相关不良事件（AE），以及整个研究期间的严重不良事件（SAE）和新出现的慢性疾病（NOCI）。
免疫原性的符合方案人群包括每组 40 名参与者。在两组中，第一剂 MenACWY-TT 诱导了针对所有疫苗血清型的 92.5-100%的 rSBA VRR 和 55.6-77.1%的 hSBA VRR。接种第二剂 MenACWY-TT 后，所有参与者均产生高反应，针对所有疫苗血清型的 rSBA 和 hSBA VRR 均为 73.0-100%。与基线水平相比，两组中每个血清型组的 rSBA 和 hSBA 几何平均滴度均升高（幅度不同，但≥13.1 倍）。≥2.0μg/ml 的多糖抗体浓度在≥84.4%的参与者中被检测到，两组之间相似。两组之间的疫苗相关和非疫苗相关不良事件的发生率相似。我们在高危组的 4/43 名参与者和对照组的 1/43 名参与者中记录了 SAE（均与疫苗无关）。未报告新出现的慢性疾病。
在这项描述性研究中，MenACWY-TT 在脾脏功能受损的儿童和青少年以及健康对照中诱导了相似的功能和体液免疫反应，且具有临床可接受的安全性。
