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Gamma-Irradiated Non-Capsule Group B Streptococcus Promotes T-Cell Dependent Immunity and Provides a Cross-Protective
Yong Zhi1, Fengjia Chen2, Guangxu Cao1
1Department of Obstetrics and Gynecology, Shanghai East Hospital, School of Medicine, Tongji University, Shanghai 200092, China.
Insights
Gamma radiation inactivated Group B Streptococcus (GBS) vaccines show enhanced immunogenicity and protective efficacy against neonatal sepsis and pneumonia. This approach offers a promising strategy for developing universal GBS vaccines.
Area of Science:
- Immunology
- Microbiology
- Vaccinology
Background:
- Group B Streptococcus (GBS) is a major cause of neonatal sepsis and pneumonia, with increasing disease burdens in adults.
- Current intrapartum antibiotic prophylaxis (IAP) is insufficient to curb rising GBS infection rates.
- Inactivating GBS via gamma radiation preserves antigenicity while eliminating replication, offering a potential vaccine strategy.
Purpose of the Study:
- To evaluate the immunogenicity and protective efficacy of gamma radiation-inactivated GBS (Rad-GBS) compared to formalin-inactivated GBS (Che-GBS).
- To assess the potential of Rad-GBS as a universal vaccine candidate against invasive GBS infections.
Main Methods:
- GBS strains were inactivated using gamma radiation (Rad-GBS) or formalin (Che-GBS).
- Immunogenicity was assessed by measuring immune cell responses (BMDCs, CD4+ T cells) and antibody production in mice.
- Protective efficacy was determined through challenge studies with virulent GBS strains and adoptive transfer experiments.
Main Results:
- Rad-GBS demonstrated superior immunogenicity compared to Che-GBS, inducing higher expression of costimulatory molecules and stronger CD4+ T cell responses (IFN-γ+, IL-17A+).
- Mice immunized with Rad-GBS showed significant protection against GBS challenge, mediated by antibodies and T cells.
- Rad-GBS induced cross-protection against multiple GBS serotypes, evidenced by enhanced opsonophagocytic killing activity.
Conclusions:
- Gamma radiation is an effective method for inactivating GBS while preserving key antigenic epitopes for vaccine development.
- Rad-GBS elicits robust cellular and humoral immune responses, providing significant protection against invasive GBS disease.
- Inactivated whole-cell GBS vaccines represent a viable strategy for developing universal vaccines against GBS infections.
Abstract:
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 CD4+IL-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.
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