Maternal immunization against group B Streptococcus: Immune correlates, microbiome trade-offs, and global implementation challenges.

Group B Streptococcus (GBS) remains a leading cause of neonatal sepsis, meningitis, stillbirth, and long-term neurodevelopmental impairment worldwide. Although intrapartum antibiotic prophylaxis (IAP) has substantially reduced early-onset GBS disease in high-income settings and remains an effective and evidence-based intervention, it does not prevent late-onset disease, maternal colonization, or GBS-associated stillbirths, and its implementation is challenging in many low- and middle-income countries (LMICs). Maternal vaccination has therefore emerged as a promising complementary strategy to achieve broader, more equitable prevention of GBS disease. This review critically examines current progress in maternal GBS vaccine development by integrating three interrelated dimensions that will shape future vaccine impact: immune correlates of protection, microbiome-related trade-offs of existing antibiotic-based prevention strategies, and global implementation challenges. We highlight recent advances and remaining uncertainties in defining serological and functional immune correlates required for regulatory decision-making, discuss emerging evidence on microbiome perturbations associated with peripartum antibiotic exposure while emphasizing their currently uncertain clinical significance, and analyze operational and policy considerations relevant to vaccine introduction in LMICs. By moving beyond descriptive summaries of the vaccine development pipeline, this review provides an integrated immunological, biological, and implementation-focused framework to inform vaccine evaluation, regulatory pathways, and policy decisions as maternal GBS vaccines approach licensure and global deployment.