Strategies to Prevent Early and Late-Onset Group B Streptococcal Infection via Interventions in Pregnancy

Abstract

Group B Streptococcus is a Gram-positive bacterium that typically colonizes 10-30% of pregnant women, causing chorioamnionitis, preterm birth, and stillbirth, as well as neonatal sepsis and meningitis with early-onset disease (EOD) or late-onset disease (LOD) due to ascending infection or transmission during delivery. While there are some differences between EOD and LOD in terms of route of transmission, risk factors, and serotypes, the only preventive approach currently is maternal intrapartum antibiotic prophylaxis (IAP) which will not be able to fully address the burden of the disease since this has no impact on LOD. Probiotics and immunization in pregnancy may be more effective than IAP for both EOD and LOD. There is mixed evidence of probiotic effects on the prevention of GBS colonization, and the data from completed and ongoing clinical trials investigating different GBS vaccines are promising. Current vaccine candidates target bacterial proteins or the polysaccharide capsule and include trivalent, tetravalent, and hexavalent protein-polysaccharide conjugate vaccines. Some challenges in developing novel GBS vaccines include the lack of a correlate of protection, the potential for serotype switching, a need to understand interactions with other vaccines, and optimal timing of administration in pregnancy to maximize protection for both term and preterm infants.

Keywords: early-onset GBS disease; group B Streptococcus; infection; late-onset GBS disease; pregnancy; prenatal immunization.

Figure 1

Summary of GBS vaccine products timeline. This figure describes the timeline of clinical trials in late-stage clinical development. While three phase II trials are on-going, five have been completed and data are publicly available for three studies. Among three ongoing trials, one for multivalent GBS vaccine has phase I and II combined trial; note phase I and phase II study population differs by gestation weeks. Promising results from the completed studies and pending results from on-going studies increase the likelihood of maternal immunization against GBS to prevent GBS infections among mothers and their infants.

Figure 2

Summary of GBS vaccine target population by gestational period for vaccine administration. As of 5 August 2022, seven phase I and II trials for trivalent and multivalent conjugate and Alpha-like protein subunits vaccines against GBS in the US National Library of Medicine’s Clinical Trial database were found; of these, two phase II studies were listed in the EU Clinical Trials Register.