Streptococcus agalactiae (Group B streptococcus or GBS) is a leading cause of neonatal and infant sepsis and meningitis globally. GBS is also associated with maternal sepsis, stillbirths and preterm births. Babies up to 3 months old are most at risk of GBS infection, particularly if they are born premature, before 37 weeks.

While intrapartum antibiotic prophylaxis (IAP) reduces early-onset GBS disease, it does not prevent late-onset disease, stillbirth, or maternal infection, and it remains challenging to implement in many low- and middle-income countries due to limited access to screening and antibiotics.

Vaccines for use in pregnancy are in development, and maternal immunization has been a priority area for the Product Development for Vaccines Advisory Committee (PDVAC) since its establishment in 2014, given the substantial global disease burden, particularly in low- and middle-income countries. GBS vaccines are also identified as a key target in the WHO Defeating Meningitis by 2030 roadmap. These vaccines aim to generate protective maternal antibodies that cross the placenta and protect newborns during the first months of life. 

WHO has developed preferred product characteristics, roadmaps, and policy-relevant analyses related to GBS vaccine development. These resources are intended to guide vaccine developers, donors, and policymakers in aligning product design, clinical evaluation, and implementation strategies. The objective is to accelerate the development and licensure of safe, effective, and affordable maternal GBS vaccines. These vaccines should be suitable for use in all settings, including low-resource environments.

Global genomic analyses, including the JUNO study, show that invasive GBS is dominated by a limited set of capsular polysaccharide (CPS) serotypes (Ia, Ib, II, III and V) accounting for 93–99% of disease worldwide and closely linked to specific clonal lineages, notably the hypervirulent CC17, which is disproportionately associated with late-onset disease and meningitis. Emerging data indicate greater strain diversity in low- and middle-income countries, alongside reduced prevalence of serotype III and CC17 in some settings. These data support projected high vaccine coverage for hexavalent CPS-conjugate vaccines, which extend these five dominant serotypes with one additional serotype. Additionally, key protein vaccine targets, particularly alpha-like proteins (Alp family), are widely conserved across strains, typically with one dominant protein per isolate and lineage-associated expression, suggesting the potential for broad, near-universal strain coverage with multicomponent protein-based vaccines.

The inverse association between maternal anti-CPS antibody concentrations and infant invasive GBS risk has supported the development of multivalent CPS–protein conjugate vaccines. The most advanced candidate is an investigational hexavalent CRM197-conjugate vaccine (GBS6) developed by Pfizer. This candidate has shown acceptable safety and immunogenicity in phase 2 studies in pregnancy, including in women living with HIV, with no evidence of interference when co-administered with Tdap vaccine. The vaccine is currently being evaluated in a global phase 3 efficacy trial (BEATRIX, NCT07160244) A second hexavalent conjugate vaccine candidate, IVT GBS-06, developed by Inventprise in partnership with PATH and covering serotypes Ia, Ib, II, III, V and VII, is completing phase 1/2 evaluation.

Naturally acquired infant IgG to Rib and Alp1 N-terminal domains has been associated with reduced risk of invasive GBS disease, supporting the relevance of Alp proteins as vaccine targets. A recombinant protein-based candidate developed by MinervaX , GBS-AlpN, also referred to as GBS-NN/NN2, incorporates N-terminal domains of AlphaC, Rib, Alp1 and Alp2/3. Recent clinical studies show that GBS-AlpN is well tolerated, induces functional antibodies with cross-strain activity, and has demonstrated acceptable safety and immunogenicity profiles in pregnant women and their infants, including women living with HIV, supporting further clinical development.

Pre-licensure clinical efficacy trials for maternal GBS vaccines face significant logistical and sample-size challenges, making a licensure pathway based on correlate of protection the most feasible approach. For this reason, WHO and partners are exploring a licensure pathway based on serological thresholds of risk reduction (SToRR; antibody levels at birth associated with reduced risk of infant invasive GBS disease) supported by post-licensure studies of effectiveness, safety and public health impact.

This approach is supported by WHO consultations and a consistent body of international seroepidemiological case–control studies. Early analyses demonstrated an inverse relationship between cord blood serotype-specific anti-CPS IgG concentrations and the risk of invasive disease in young infants, establishing a biological basis for antibody-mediated protection, and identifying cord blood IgG as the most appropriate immunological endpoint. More recent data from South Africa, the United States, and large multi-country analyses further define quantitative associations between antibody levels and disease risk, with thresholds varying by serotype and by timing of disease onset.