PDF(Pubmed)
Abstract：
Group B Streptococcus (Streptococcus agalactiae or GBS) is the leading infectious cause of neonatal mortality, causing roughly 150,000 infant deaths and stillbirths annually across the globe. Approximately 20% of pregnant women are asymptomatically colonized by GBS, which is a major risk factor for severe fetal and neonatal infections as well as preterm birth, low birth weight, and neurodevelopmental abnormalities. Current clinical interventions for GBS infection are limited to antibiotics, and no vaccine is available. We previously described VAX-A1 as a highly effective conjugate vaccine against group A Streptococcus that is formulated with three antigens, SpyAD, streptolysin O, and C5a peptidase (ScpA). ScpA is a surface-expressed, well-characterized GAS virulence factor that shares nearly identical sequences with the lesser studied GBS homolog ScpB. Here, we show that GBS C5a peptidase ScpB cleaves human complement factor C5a and contributes to disease severity in the murine models of pneumonia and sepsis. Furthermore, antibodies elicited by GAS C5a peptidase bind to GBS in an ScpB-dependent manner, and VAX-A1 immunization protects mice against lethal GBS heterologous challenge. These findings support the contribution of ScpB to GBS virulence and underscore the importance of choosing vaccine antigens; a universal GAS vaccine such as VAX-A1 whose formulation includes GAS C5a peptidase may have additional benefits through some measure of cross-protection against GBS infections.
摘要：
B族链球菌（无乳链球菌或GBS）是新生儿死亡的主要传染性原因，每年在全球造成大约15万婴儿死亡和死产。大约20％的孕妇被GBS无症状地定植，这是严重的胎儿和新生儿感染以及早产的主要危险因素，低出生体重,神经发育异常.目前GBS感染的临床干预措施仅限于抗生素，没有疫苗可用。我们先前将VAX-A1描述为针对A组链球菌的高效结合疫苗，该疫苗与三种抗原一起配制，SpyAD,链球菌素O,和C5a肽酶(ScpA)。ScpA是表面表达的，表征良好的GAS毒力因子，与研究较少的GBS同源物ScpB共享几乎相同的序列。这里,我们显示GBSC5a肽酶ScpB切割人补体因子C5a,并在肺炎和脓毒症鼠模型中导致疾病严重程度.此外，GASC5a肽酶引发的抗体以ScpB依赖性方式与GBS结合，和VAX-A1免疫保护小鼠免受致死的GBS异源攻击。这些发现支持ScpB对GBS毒力的贡献，并强调了选择疫苗抗原的重要性；通用GAS疫苗，如VAX-A1，其制剂包括GASC5a肽酶，可能会通过某种措施对GBS感染的交叉保护具有额外的益处。
