Development and evaluation of a multi-epitope subunit vaccine against group B Streptococcus infection

Area of Science:

• Immunology
• Vaccinology
• Microbial Pathogenesis

Background:

• Group B Streptococcus (GBS) is a significant multi-host pathogen, posing life-threatening risks, particularly to newborns.
• Vaccination strategies targeting multiple GBS serotypes are crucial for effective long-term infection control.
• Developing a broadly protective GBS vaccine remains a public health priority.

Purpose of the Study:

• To design and evaluate a novel multivalent multiepitope-based subunit vaccine (MVSA) against Group B Streptococcus (GBS).
• To assess the immunogenicity and protective efficacy of MVSA through in silico and in vivo studies.
• To explore the potential of MVSA for broad population coverage against diverse GBS serotypes.

Main Methods:

• Development of a comprehensive in silico epitope-prediction workflow to identify vaccine candidates.
• Selection of 11 epitopes from confirmed antigenic, virulent-associated, surface-exposed, and conserved GBS proteins across ten serotypes.
• Validation of MVSA efficacy using a mouse model, including antibody titration, splenocyte proliferation assays, and lethal-dose challenge studies.
• In vitro assessment of polyclonal antibodies against MVSA for growth inhibition of multiple GBS serotypes and passive protection assays.

Main Results:

• In silico analysis predicted MVSA's potential to induce strong immune responses and achieve worldwide population coverage.
• Immunization with MVSA in mice resulted in high antibody titers and significant splenocyte proliferation.
• MVSA demonstrated 100% protection against lethal GBS challenge in mice after three vaccinations.
• Polyclonal antibodies against MVSA inhibited GBS growth in vitro across six key serotypes and provided 100% protection in naive mice against lethal GBS challenge.

Conclusions:

• The multivalent multiepitope-based subunit vaccine (MVSA) is a promising candidate for an efficacious GBS vaccine.
• Both active immunization with MVSA and passive immunity conferred by its antibodies provide robust protection against GBS.
• MVSA's ability to target multiple serotypes and induce strong immune responses suggests its potential for broad clinical application against GBS infections.