From Centre pour le Développement des Vaccins du Mali, Bamako (M.D.T., S.O.S., F.D., F.C.H., A.T.); the Center for Vaccine Development and Global Health, University of Maryland School of Medicine, Baltimore (M.D.T.); PATH, Seattle (A.N., L.M., N.H., I.S., Y.T., M.R.A.); the Serum Institute of India, Pune (A.C., S.S.P., F.M.L., R.M.D., D.K., P.S.K.); and the Vaccine Evaluation Unit, Public Health England, Manchester Royal Infirmary, Manchester, United Kingdom (K.T.-P., R.B.).
N Engl J Med. 2021 Jun 3;384(22):2115-2123. doi: 10.1056/NEJMoa2013615.
serogroups A, B, C, W, X, and Y cause outbreaks of meningococcal disease. Quadrivalent conjugate vaccines targeting the A, C, W, and Y serogroups are available. A pentavalent vaccine that also includes serogroup X (NmCV-5) is under development.
We conducted a phase 2, observer-blinded, randomized, controlled trial involving Malian children 12 to 16 months of age. Participants were assigned in a 2:2:1 ratio to receive nonadjuvanted NmCV-5, alum-adjuvanted NmCV-5, or the quadrivalent vaccine MenACWY-D, administered intramuscularly in two doses 12 weeks apart. Participants were followed for safety for 169 days. Immunogenicity was assessed with an assay for serum bactericidal antibody (SBA) with rabbit complement on days 0, 28, 84, and 112.
A total of 376 participants underwent randomization, with 150 assigned to each NmCV-5 group and 76 to the MenACWY-D group; 362 participants received both doses of vaccine. A total of 1% of the participants in the nonadjuvanted NmCV-5 group, 1% of those in the adjuvanted NmCV-5 group, and 4% of those in the MenACWY-D group reported local solicited adverse events; 6%, 5%, and 7% of the participants, respectively, reported systemic solicited adverse events. An SBA titer of at least 128 was seen in 91 to 100% (for all five serotypes) of the participants in the NmCV-5 groups and in 36 to 99% (excluding serogroup X) of those in the MenACWY-D group at day 84 (before the second dose); the same threshold was met in 99 to 100% (for all five serotypes) of the participants in the NmCV-5 groups and in 92 to 100% (excluding serogroup X) of those in the MenACWY-D group at day 112. Immune responses to the nonadjuvanted and adjuvanted NmCV-5 formulations were similar.
No safety concerns were identified with two doses of NmCV-5. A single dose of NmCV-5 elicited immune responses that were similar to those observed with two doses of MenACWY-D. Adjuvanted NmCV-5 provided no discernible benefit over nonadjuvanted NmCV-5. (Funded by the U.K. Foreign, Commonwealth, and Development Office; ClinicalTrials.gov number, NCT03295318.).
A、B、C、W、X 和 Y 血清群可引起脑膜炎球菌病暴发。针对 A、C、W 和 Y 血清群的四价结合疫苗已上市。一种包含 X 血清群（NmCV-5）的五价疫苗正在研发中。
我们开展了一项 2 期、观察者设盲、随机、对照试验，纳入了年龄为 12 至 16 个月的马里儿童。参与者按照 2:2:1 的比例随机分配，分别接受非佐剂 NmCV-5、佐剂 NmCV-5 或四价疫苗 MenACWY-D，肌肉内注射，间隔 12 周接种 2 剂。参与者接受安全性随访 169 天。采用兔补体血清杀菌抗体（SBA）测定法在第 0、28、84 和 112 天评估免疫原性。
共有 376 名参与者接受了随机分组，其中 150 名参与者被分配到非佐剂 NmCV-5 组和佐剂 NmCV-5 组，每组各 150 名；76 名参与者被分配到 MenACWY-D 组。非佐剂 NmCV-5 组、佐剂 NmCV-5 组和 MenACWY-D 组各有 1%的参与者报告局部不良事件，分别为 1%、1%和 4%；各有 6%、5%和 7%的参与者报告全身不良事件。在第 84 天（第二剂之前），NmCV-5 组的所有参与者（所有五种血清型）的 SBA 滴度均达到至少 128，MenACWY-D 组的参与者（不包括血清群 X）为 36%至 99%；在第 112 天，NmCV-5 组的所有参与者（所有五种血清型）的 SBA 滴度均达到 99%至 100%，MenACWY-D 组的参与者（不包括血清群 X）为 92%至 100%。非佐剂和佐剂 NmCV-5 制剂的免疫应答相似。
两剂 NmCV-5 无安全性问题。一剂 NmCV-5 可引起与两剂 MenACWY-D 相似的免疫应答。佐剂 NmCV-5 并未比非佐剂 NmCV-5 提供明显益处。（由英国国际发展部资助；ClinicalTrials.gov 编号，NCT03295318。）
