GSK, via Fiorentina 1, 53100 Siena, Italy.
Meningococcal Reference Unit, Public Health England, Manchester Royal Infirmary, Oxford Road, Manchester M13 9WL, United Kingdom.
Vaccine. 2020 Nov 3;38(47):7542-7550. doi: 10.1016/j.vaccine.2020.09.050. Epub 2020 Oct 7.
The multicomponent meningococcal serogroup B vaccine (4CMenB) is currently indicated for active immunization against invasive meningococcal disease caused by Neisseria meningitidis serogroup B (MenB). However, genes encoding the 4CMenB antigens are also variably present and expressed in strains belonging to other meningococcal serogroups. In this study, we evaluated the ability of antibodies raised by 4CMenB immunisation to induce complement-mediated bactericidal killing of non-MenB strains.
A total of 227 invasive non-MenB disease isolates were collected between 1 July 2007 and 30 June 2008 from England and Wales, France, and Germany; 41 isolates were collected during 2012 from Brazil. The isolates were subjected to genotypic analyses. A subset of 147 isolates (MenC, MenW and MenY) representative of the meningococcal genetic diversity of the total sample were tested in the human complement serum bactericidal antibody assay (hSBA) using sera from infants immunised with 4CMenB.
Serogroup and clonal complex repertoires of non-MenB isolates were different for each country. For the European panel, MenC, MenW and MenY isolates belonged mainly to ST-11, ST-22 and ST-23 complexes, respectively. For the Brazilian panel, most MenC and MenW isolates belonged to the ST-103 and ST-11 complexes, respectively, and most MenY isolates were not assigned to clonal complexes. Of the 147 non-MenB isolates, 109 were killed in hSBA, resulting in an overall coverage of 74%.
This is the first study in which 147 non-MenB serogroup isolates have been analysed in hSBA to evaluate the potential of a MenB vaccine to cover strains belonging to other serogroups. These data demonstrate that antibodies raised by 4CMenB are able to induce bactericidal killing of 109 non-MenB isolates, representative of non-MenB genetic and geographic diversity. These findings support previous evidence that 4CMenB immunisation can provide cross-protection against non-MenB strains in infants, which represents an added benefit of 4CMenB vaccination.
多组份脑膜炎奈瑟菌 B 型疫苗（4CMenB）目前被用于主动免疫预防由脑膜炎奈瑟菌 B 血清型（MenB）引起的侵袭性脑膜炎球菌病。然而，编码 4CMenB 抗原的基因也在属于其他脑膜炎奈瑟菌血清型的菌株中存在和表达。在这项研究中，我们评估了 4CMenB 免疫产生的抗体诱导补体介导的非 MenB 菌株杀菌杀伤的能力。
2007 年 7 月 1 日至 2008 年 6 月 30 日期间，从英国和威尔士、法国和德国共收集了 227 株侵袭性非 MenB 疾病分离株；2012 年期间从巴西收集了 41 株分离株。分离株进行了基因分析。从接种了 4CMenB 的婴儿血清中选择了代表总样本脑膜炎奈瑟菌遗传多样性的 147 株分离株（MenC、MenW 和 MenY）的亚组，在人补体血清杀菌抗体测定（hSBA）中进行了检测。
非 MenB 分离株的血清组和克隆复合体谱因国家而异。对于欧洲组，MenC、MenW 和 MenY 分离株分别主要属于 ST-11、ST-22 和 ST-23 复合体。对于巴西组，大多数 MenC 和 MenW 分离株分别属于 ST-103 和 ST-11 复合体，而大多数 MenY 分离株未被分配到克隆复合体。在 147 株非 MenB 分离株中，有 109 株在 hSBA 中被杀死，总覆盖率为 74%。
这是第一项分析 147 株非 MenB 血清型分离株在 hSBA 中以评估 MenB 疫苗覆盖其他血清型菌株的潜力的研究。这些数据表明，4CMenB 免疫产生的抗体能够诱导杀菌杀伤 109 株非 MenB 分离株，这些分离株代表了非 MenB 遗传和地理多样性。这些发现支持了之前的证据，即 4CMenB 免疫接种可在婴儿中提供针对非 MenB 菌株的交叉保护，这是 4CMenB 疫苗接种的一个额外益处。
