Vaccine Research and Development, Pfizer, Pearl River, New York.
J Infect Dis. 2019 Jun 5;220(1):105-115. doi: 10.1093/infdis/jiz062.
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.
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.
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.
The findings support the ongoing clinical evaluation of maternal GBS6 vaccination as a potential alternative method to prevent GBS disease in infants.
B 群链球菌(GBS)可导致新生儿罹患严重疾病,常导致终生神经损伤或死亡。在分娩前对孕妇进行预防性疫苗接种可提供全面保护,因为早期和晚期疾病以及母体并发症都可能得到解决。
使用通过对最近分离出的导致侵袭性新生儿 GBS 疾病的全球 GBS 分离株的全基因组测序产生的监测数据设计荚膜多糖结合疫苗 GBS6。荚膜多糖被分离出来,使用高碘酸钠氧化,然后通过还原胺化在二甲基亚砜中与 CRM197 结合。在多重 Luminex 免疫球蛋白 G(IgG)测定和调理吞噬活性测定中测量了小鼠和恒河猴中的免疫反应。
单独和组合使用时,优化的缀合物在小鼠和恒河猴中具有免疫原性,诱导介导调理吞噬杀伤的 IgG 抗体。在交配前用 GBS6 对鼠母体进行主动免疫可使幼仔免受致命的 GBS 攻击的特异性保护。向母体被动给予针对特定血清型的 IgG 单克隆抗体证明了抗荚膜多糖 IgG 本身足以提供保护。
这些发现支持对母体 GBS6 疫苗接种进行正在进行的临床评估,作为预防婴儿 GBS 疾病的潜在替代方法。