A Novel Hexavalent Capsular Polysaccharide Conjugate Vaccine (GBS6) for the Prevention of Neonatal Group B Streptococcal Infections by Maternal Immunization
A Novel Hexavalent Capsular Polysaccharide Conjugate Vaccine (GBS6) for the Prevention of Neonatal Group B Streptococcal Infections by Maternal Immunization
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DOI：
10.1093/infdis/jiz062
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发表时间：
2019-07-01
影响因子：
6.4
通讯作者：
Anderson, Annaliesa S.
中科院分区：
文献类型：
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作者：
Buurman, Ed T.;Timofeyeva, Yekaterina;Anderson, Annaliesa S.
背景资料。B组链球菌(GBS)会导致新生儿患上严重疾病，通常会导致终生神经损伤或死亡。孕妇产前预防性接种疫苗可以提供全面的保护，因为早发和晚发疾病和孕产妇并发症有可能得到解决。胶囊多糖结合疫苗GBS6是利用对最近恢复的导致侵袭性新生儿GBS疾病的全球GBS分离株进行全基因组测序所产生的监测数据设计的。提取胶囊多糖，用高碘酸钠氧化，在二甲基亚砜中还原胺化偶联到CRM197上。用免疫球蛋白G(Ig G)和吞噬细胞活性测定了小鼠和猕猴的免疫应答。优化的结合物在小鼠和猕猴体内是免疫原性的，单独和联合，诱导出介导吞噬细胞杀伤的免疫球蛋白抗体。在交配前用GBS6主动免疫小鼠，可使幼鼠免受GBS的致死攻击，从而获得特定的血清型保护。被动给药后的保护作用表明，仅抗囊多糖免疫球蛋白抗体就足以起到保护作用。这些发现支持正在进行的对孕妇接种GBS6疫苗作为预防婴儿GBS疾病的潜在替代方法的临床评估。
Background. Group B streptococcus (GBS) causes serious diseases in newborn infants, often resulting in lifelong neurologic impairments or death. Prophylactic vaccination of pregnant women prior to delivery could provide comprehensive protection, as early onset and late-onset disease and maternal complications potentially could be addressed.Methods. Capsular polysaccharide conjugate vaccine GBS6 was designed using surveillance data yielded by whole-genome sequencing of a global collection of recently recovered GBS isolates responsible for invasive neonatal GBS disease. Capsular polysaccharides were isolated, oxidized using sodium periodate, and conjugated to CRM197 by reductive amination in dimethyl sulfoxide. Immune responses in mice and rhesus macaques were measured in a multiplex Luminex immunoglobulin G (IgG) assay and opsonophagocytic activity assays.Results. The optimized conjugates were immunogenic, alone and in combination, in mice and rhesus macaques, inducing IgG antibodies that mediated opsonophagocytic killing. Active immunization of murine dams with GBS6 prior to mating resulted in serotype-specific protection of pups from a lethal challenge with GBS. Protection following passive administration of serotype-specific IgG monoclonal antibodies to dams demonstrated conclusively that anticapsular polysaccharide IgG alone is sufficient for protection.Conclusions. The findings support the ongoing clinical evaluation of maternal GBS6 vaccination as a potential alternative method to prevent GBS disease in infants.