Zhi Yong, Chen Fengjia, Cao Guangxu, Li Fang
Department of Obstetrics and Gynecology, Shanghai East Hospital, School of Medicine, Tongji University, Shanghai 200092, China.
Research Division for Radiation Science, Korea Atomic Energy Research Institute, Jeongeup 56212, Republic of Korea.
Pharmaceuticals (Basel). 2023 Feb 20;16(2):321. doi: 10.3390/ph16020321.
Group B Streptococcus (GBS) is a Gram-positive bacterium commonly found in the genitourinary tract and is also a leading cause of neonatal sepsis and pneumonia. Despite the current antibiotic prophylaxis (IAP), the disease burdens of late-onset disease in newborns and non-pregnant adult infections are increasing. Recently, inactivation of the pathogens via gamma radiation has been proven to eliminate their replication ability but cause less damage to the antigenicity of the key epitopes. In this study, the non-capsule GBS strain was inactivated via radiation (Rad-GBS) or formalin (Che-GBS), and we further determined its immunogenicity and protective efficacy as vaccines. Notably, Rad-GBS was more immunogenic and gave rise to higher expression of costimulatory molecules in BMDCs in comparison with Che-GBS. Flow cytometric analysis revealed that Rad-GBS induced a stronger CD4 IFN-γ and CD4IL-17A population in mice. The protective efficacy was measured through challenge with the highly virulent strain CNCTC 10/84, and the adoptive transfer results further showed that the protective role is reversed by functionally neutralizing antibodies and T cells. Finally, cross-protection against challenges with prevalent serotypes of GBS was induced by Rad-GBS. The higher opsonophagocytic killing activity of sera against multiple serotypes was determined in sera from mice immunized with Rad-GBS. Overall, our results showed that the inactivated whole-cell encapsulated GBS could be an alternative strategy for universal vaccine development against invasive GBS infections.
B族链球菌（GBS）是一种革兰氏阳性细菌，常见于泌尿生殖道，也是新生儿败血症和肺炎的主要病因。尽管目前有抗生素预防措施（IAP），但新生儿迟发性疾病和非妊娠成人感染的疾病负担仍在增加。最近，已证明通过伽马辐射使病原体失活可消除其复制能力，但对关键表位的抗原性造成的损害较小。在本研究中，通过辐射（Rad-GBS）或福尔马林（Che-GBS）使非荚膜GBS菌株失活，我们进一步确定了其作为疫苗的免疫原性和保护效果。值得注意的是，与Che-GBS相比，Rad-GBS具有更强的免疫原性，并在骨髓来源的树突状细胞（BMDCs）中引起共刺激分子的更高表达。流式细胞术分析显示，Rad-GBS在小鼠中诱导出更强的CD4 IFN-γ和CD4IL-17A细胞群。通过用高毒力菌株CNCTC 10/84进行攻击来测量保护效果，过继转移结果进一步表明，功能中和抗体和T细胞可逆转这种保护作用。最后，Rad-GBS诱导了对GBS流行血清型攻击的交叉保护。在用Rad-GBS免疫的小鼠血清中，测定了血清对多种血清型的更高调理吞噬杀伤活性。总体而言，我们的结果表明，灭活的全细胞包膜GBS可能是开发针对侵袭性GBS感染的通用疫苗的替代策略。
