Preclinical Immunogenicity of a 6-Valent GBS Glycoconjugate Vaccine from a Repeat-Dose GLP Toxicology Study

Area of Science:

• Vaccinology
• Microbiology
• Immunology

Background:

• Group B Streptococcus (GBS) causes severe perinatal infections in neonates and infants, leading to sepsis, meningitis, and mortality.
• Maternal immunization is a promising strategy to prevent GBS infections, especially in low- and middle-income countries (LMICs).
• Current GBS vaccines are not licensed, highlighting the need for effective interventions.

Purpose of the Study:

• To present a novel hexavalent GBS vaccine candidate (GBS-06) targeting serotypes Ia, Ib, II, III, V, and VII.
• To evaluate the immunogenicity and safety of GBS-06 in a preclinical toxicology study.
• To assess the potential of GBS-06 as a cost-effective intervention with broad global coverage.

Main Methods:

• Development of a 6-valent conjugate vaccine (GBS-06) using a novel hydrazide-polyethylene glycol-hydrazide (HZ-PEG-HZ) linker.
• The vaccine links six GBS polysaccharides (PS) to a recombinant cross-reactive material 197 (rCRM197) carrier protein.
• A repeat-dose Good Laboratory Practice (GLP) toxicology study was conducted in rabbits at the highest clinical dose (20 µg).

Main Results:

• GBS-06 induced robust anti-capsular polysaccharide-specific IgG responses against all six targeted serotypes.
• The highest antibody geometric mean concentrations (GMCs) were observed on Day 49, following the third vaccine dose.
• The study demonstrated strong immunogenicity with no adverse findings reported in the toxicology assessment.

Conclusions:

• This study is the first to demonstrate successful immunogenicity using the HZ-PEG-HZ linker for GBS glycoconjugate vaccine development.
• The GBS-06 vaccine candidate shows potential for broad protection (99% against circulating serotypes) and efficacy.
• Positive preclinical data support the advancement of GBS-06 into clinical trials for maternal immunization programs.