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B 群脑膜炎奈瑟菌疫苗 - 基因组学揭示葡萄牙株的覆盖范围。

Vaccines against Neisseria meningitidis serogroup B strains - What does genomics reveal on the Portuguese strain's coverage.

机构信息

National Reference Laboratory for Neisseria meningitidis, Department of Infectious Diseases, National Institute of Health (INSA), 1649-016 Lisbon, Portugal.

Laboratório de Biomatemática - Instituto de Medicina Preventiva e Saúde Pública, 1649-028 Lisbon, Portugal.

出版信息

Vaccine. 2022 Aug 5;40(33):4772-4779. doi: 10.1016/j.vaccine.2022.06.038. Epub 2022 Jun 29.

DOI:10.1016/j.vaccine.2022.06.038
PMID:35778280
Abstract

In Portugal, Neisseria meningitidis serogroup B (MenB) is the most common serogroup causing invasive meningococcal disease. To protect against MenB disease two protein based MenB vaccines are available in Portugal, the 4CMenB that was licenced in 2014 and included in the routine immunization program in October 2020, and the bivalent rLP2086 vaccine licensed in 2017. The aim of this study was to predict the coverage of the 4CMenB and rLP2086 vaccines against Portuguese isolates of Neisseria meningitidis sampled between 2012 and 2019 and to evaluate the diversity of vaccine antigens based on genomic analysis. Whole-genome sequence data from 324 Portuguese Neisseria meningitidis isolates were analysed. To predict strain coverage by 4CMenB and rLP2086, vaccine antigen reactivity was assessed using the MenDeVar index available on the PubMLST Neisseria website. This study included 235 (75.6%) MenB isolates of all invasive MenB strains reported between 2012 and 2019. Moreover, 89 non MenB isolates sampled in the same period, enrolling 68 from invasive disease and 21 from healthy carriers, were also studied. The predicted strain coverage of MenB isolates was 73.5% (95% CI: 64.8%-81.2%) for 4CMenB and 100% for rLP2086. Predicted strain coverage by 4CMenB in the age group from 0 to 4 years old, was 73.9%. Most of MenB isolates were covered by a single antigen (85.4%), namely fHbp (30.3%), P1.4 (29.2%), and NHBA (24.7%). In Portugal, the most prevalent peptides in MenB isolates were: P1.4 (16.2%), NHBA peptide 2 (14.0%), and fHbp peptide 14 (7.2%), from 4CMenB and fHbp peptide 19 (10.6%) from rLP2086. No significant temporal trends were observed concerning the distribution and diversity of vaccine antigen variants. 4CMenB and rLP2086 vaccines showed potential coverage for isolates regardless serogroup. The use of both vaccines should be considered to control possible outbreaks caused by serogroups with no vaccine available.

摘要

在葡萄牙,脑膜炎奈瑟菌 B 群(MenB)是导致侵袭性脑膜炎球菌病最常见的血清群。为了预防 MenB 疾病,葡萄牙有两种基于蛋白质的 MenB 疫苗,分别是 2014 年获得许可并于 2020 年 10 月纳入常规免疫计划的 4CMenB,以及 2017 年获得许可的 bivalent rLP2086 疫苗。本研究旨在预测 4CMenB 和 rLP2086 疫苗对 2012 年至 2019 年间采集的葡萄牙脑膜炎奈瑟菌分离株的覆盖范围,并根据基因组分析评估疫苗抗原的多样性。对 324 株葡萄牙脑膜炎奈瑟菌分离株的全基因组序列数据进行了分析。为了预测 4CMenB 和 rLP2086 的菌株覆盖率,使用 PubMLST Neisseria 网站上提供的 MenDeVar 指数评估了疫苗抗原的反应性。本研究包括 2012 年至 2019 年间报告的所有侵袭性 MenB 菌株中 235 株(75.6%)MenB 分离株。此外,还研究了同期采集的 89 株非 MenB 分离株,其中 68 株来自侵袭性疾病,21 株来自健康携带者。预测的 MenB 分离株覆盖率为 4CMenB 为 73.5%(95%CI:64.8%-81.2%),rLP2086 为 100%。0 至 4 岁年龄组 4CMenB 的预测菌株覆盖率为 73.9%。大多数 MenB 分离株仅被一种抗原覆盖(85.4%),即 fHbp(30.3%)、P1.4(29.2%)和 NHBA(24.7%)。在葡萄牙,MenB 分离株中最常见的肽是:4CMenB 的 P1.4(16.2%)、NHBA 肽 2(14.0%)和 fHbp 肽 14(7.2%),rLP2086 的 fHbp 肽 19(10.6%)。疫苗抗原变体的分布和多样性没有观察到明显的时间趋势。4CMenB 和 rLP2086 疫苗对血清群无关的分离株具有潜在的覆盖能力。应考虑使用这两种疫苗来控制可能由无疫苗可用的血清群引起的暴发。

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