EBNEO COMMENTARY: SAFETY AND IMMUNOGENICITY OF GBS VACCINE IN PREGNANCY AND DETERMINATION OF A SEROCORRELATE FOR INFANT PROTECTION

COMMENTARY: 

"Group B Streptococcus (GBS) causes approximately 150,000 stillbirths and infant deaths annually worldwide.1 Infants who are exposed to maternal GBS colonization are at risk of sepsis and meningitis, which when not fatal, are associated with significant life-long morbidity.2 Accordingly, the development of a maternal GBS vaccine is a public health priority.1 A vaccine could help prevent GBS-associated morbidities and mortality. The results of this phase 2, randomized, placebo-controlled trial provide not only evidence that Pfizer’s GBS hexavalent vaccine (GBS6) is safe and immunogenic; the parallel seroepidemiology data also provide an evidence-based serocorrelate of protection that can be utilized in future studies.3

In some regions, universal GBS screening and targeted intrapartum antibiotic prophylaxis (IAP) have led to a substantial decline in cases of early-onset disease, though several limitations serve as the foundation for maternal GBS vaccine development.4 First, in many regions, IAP is not standard of care. Second, early-onset disease still persists in regions utilizing IAP due to limitations in antenatal screening. Third, a substantial portion of early-onset disease occurs among preterm infants, who may not benefit from late pregnancy screening and IAP. Fourth, IAP does not impact late-onset disease. Lastly, there are evolving concerns about the impact of IAP on maternal and neonatal dysbiosis, and selection pressure leading to colonization and infection with antibiotic-resistant organisms.5

The investigators provide reassuring data that GBS6 is safe. Maternal and infant adverse events were similar between groups and no serious adverse events were attributed to the vaccine. The vaccine was immunogenic in pregnant women and placental antibody transfer, known to be less robust for GBS compared with other pathogens, was achieved at concentrations that correlate with proposed threshold concentrations for protection against invasive infant disease. Importantly, investigators used a cross-standardized immunoassay and propose a single protective threshold that could be utilized in ongoing and future GBS vaccine research.

The study had several limitations. The study was conducted in a setting that does not use IAP, as the impact of IAP on infant infection could cloud the picture when assessing a serologic threshold of protection. Serologic estimates from low- and middle-income countries may overestimate thresholds for high-income countries. Demographics of the study cohort may limit generalizability: enrolled pregnant persons were generally young, multiparous, of Black-African race/ethnicity, and roughly one third had HIV infection. The estimated serocorrelate of protection should also be viewed with caution. Acknowledging the remarkable effort represented by this study, the serocorrelate modeling was based on measurements from only 77 cases: when broken out by 6 serotypes and early- and late-onset disease, only type III infection was represented by >10 cases. The authors emphasize that the reported serocorrelate must be better defined in future studies with different populations. Such studies are needed to address the effect of pre-existing, naturally-acquired serotype-specific antibody on vaccine response, as well as maternal morbidities that may affect placental antibody transfer. Finally, a larger set of case-control data encompassing all common serotypes and both early- and late-onset disease is needed to generate robust estimates for serotype-specific serocorrelates of protection."