Genomic characterization of invasive Neisseria meningitidis in Spain (2011/12–2022/23): expansion of clonal complex 213 and the potential threat to 4CMenB vaccine strain coverage

Invasive meningococcal disease (IMD) is associated with significant global morbidity and mortality and is addressed by conjugated polysaccharide and subcapsular vaccines. In Spain, data on 4CMenB vaccine strain coverage and antimicrobial susceptibility are limited. This study aimed to describe the genomic epidemiology, predict 4CMenB vaccine strain coverage, and assess antimicrobial susceptibility of 323 Neisseria meningitidis isolates causing IMD, collected from 57 Clinical Microbiology Laboratories in Spain over 12 years (2011/12–2022/23). Whole genome sequencing was performed to identify serogroup, clonal complex (cc), and antimicrobial resistance determinants. Vaccine strain coverage for serogroup B (MenB) isolates was predicted using the genetic Meningococcal Antigen Typing System approach. The most prevalent serogroups were B (57.9%), W (21.4%), C (10.4%), and Y (8.4%). MenB predominated throughout most seasons, except during the 2019/20 season when serogroup W peaked. Post-COVID-19 pandemic, MenB remained the most frequent (70.2%). Thirteen cc were identified among MenB isolates, with cc213 being the most prevalent (40.1%). Only 28.9% of MenB isolates were predicted to be covered by 4CMenB, with cc213 showing an exceptionally low coverage rate (5.3%) due to antigenic variants poorly targeted by the vaccine. Notably, cc213 was responsible for twice the proportion of MenB cases in 4CMenB-vaccinated versus unvaccinated. All isolates were susceptible to third generation cephalosporins, and 13.5% showed penicillin resistance. This study highlights the alarming prevalence of cc213 among MenB IMD cases in Spain and the limited 4CMenB coverage against this cc. The disproportionate representation of cc213 in vaccinated individuals underscores its potential to compromise vaccine effectiveness.侵袭性脑膜炎球菌病（Invasive meningococcal disease, IMD）与全球范围内严重的发病率和死亡率相关，目前可通过结合多糖疫苗与荚膜亚单位疫苗进行防控。在西班牙，有关4CMenB疫苗菌株覆盖范围及抗菌药物敏感性的数据较为有限。本研究旨在描述323株引发侵袭性脑膜炎球菌病的脑膜炎奈瑟菌分离株的基因组流行病学特征，预测其4CMenB疫苗菌株覆盖情况，并评估其抗菌药物敏感性；这些分离株于2011/12至2022/23年的12年间，由西班牙57个临床微生物实验室采集获得。全基因组测序被用于鉴定菌株的血清群、克隆复合体（clonal complex, cc）及抗菌药物耐药决定簇。针对血清群B型（MenB）分离株，通过基因分型脑膜炎球菌抗原分型系统（Meningococcal Antigen Typing System）方法预测其疫苗覆盖范围。最常见的血清群依次为B群（57.9%）、W群（21.4%）、C群（10.4%）及Y群（8.4%）。除2019/20季度血清群W占比达到峰值外，B群脑膜炎球菌在多数季度均为优势流行菌株。新冠疫情过后，B群脑膜炎球菌仍为最常见的分离株（占比70.2%）。在B群分离株中共鉴定出13种克隆复合体，其中以cc213最为流行（占比40.1%）。仅28.9%的B群分离株被预测可被4CMenB疫苗覆盖，而cc213的疫苗覆盖比例极低（仅5.3%），原因在于其抗原变异株难以被该疫苗靶向识别。值得注意的是，在接种4CMenB疫苗的人群中，cc213所致B群病例占比是未接种人群的两倍。所有分离株均对第三代头孢菌素敏感，另有13.5%的分离株表现出青霉素耐药性。本研究凸显了西班牙B群侵袭性脑膜炎球菌病病例中cc213的高流行率，以及4CMenB疫苗针对该克隆复合体的有限覆盖范围。cc213在接种人群中的不成比例占比，提示其可能会削弱疫苗的保护效果。