Advances towards licensure of a maternal vaccine for the prevention of invasive group B streptococcus disease in infants: a discussion of different approaches

Abstract

Group B streptococcus ( Streptococcus agalactiae , GBS) is an important cause of life-threatening disease in newborns. Pregnant women colonized with GBS can transmit the bacteria to the developing fetus, as well as to their neonates during or after delivery where infection can lead to sepsis, meningitis, pneumonia, or/and death. While intrapartum antibiotic prophylaxis (IAP) is the standard of care for prevention of invasive GBS disease in some countries, even in such settings a substantial residual burden of disease remains. A GBS vaccine administered during pregnancy could potentially address this important unmet medical need and provide an adjunct or alternative to IAP for the prevention of invasive GBS disease in neonates. A hurdle for vaccine development has been relatively low disease rates making efficacy studies difficult. Given the well-accepted inverse relationship between anti-GBS capsular polysaccharide antibody titers at birth and risk of disease, licensure using serological criteria as a surrogate biomarker represents a promising approach to accelerate the availability of a GBS vaccine.

20 million pregnant women with group B streptococcus carriage: consequences, challenges, and opportunities for prevention

“…Indeed, it has been estimated that such a trial would require 30,000–1800,000 participants, depending on vaccine efficacy and disease incidence, and would therefore require significant time and resources [37]. A recent review summarised the potential paths to licensure for GBS vaccines [43 ▪▪ ]. Compared to the conventional approval pathway, an accelerated approval pathway by regulatory authorities, such as the US Food and Drug Administration or the Medicines and Healthcare Products Regulatory Agency, might lead to licensure of a GBS vaccine based on a surrogate immunological endpoint and use in pregnant women.…”

“…Such an approach was favourably discussed during the Vaccine and Related Biological Products Advisory Committee in May 2018 and could allow licensure based on serocorrelate of protection followed by a confirmatory effectiveness study postlicensure. Alternatively, an immunological endpoint could be nested in a trial with a clinical endpoint, where trial size would be based on the clinical endpoint, and immunogenicity results could be used for accelerated approval, before efficacy estimates based on disease become available [43 ▪▪ ]. Both approaches rely on validated serological correlates of protection using standardised assays.…”

Group B Streptococcus Early-Onset Disease: New Preventive and Diagnostic Tools to Decrease the Burden of Antibiotic Use

“…More importantly, the transfer of protective IgG antibodies to the newborn via the placenta might protect the child from invasive GBS disease during the first months of life. A hexavalent GBS conjugate vaccine was recently proven safe and immunogenic in healthy adults and is currently being studied in pregnant women [ 48 ]. However, clinical efficacy studies are time-consuming and expensive due to low disease incidence.…”

“…A large range of biomarkers have been tested in the umbilical cord blood of preterm and term newborns, for example, CRP, procalcitonin (PCT), interleukins, TNF-α, interferon gamma (IFN-y), serum amyloid A (SAA), presepsin, etc. [ 48 , 49 , 50 , 51 , 52 , 53 ]. Similar to maternal serum samples, CRP does not perform well in distinguishing between infected and non-infected newborns, with low sensitivity (around 50%) across studies [ 53 ].…”

Group B Streptococcal Disease in Infants in Japan

“…49 In addition, since there are proteins that may be present in different serotypes, protein-based vaccines have the potential to provide protection across the serotype spectrum. 49 Leading vaccine candidates are expected to be licensed for maternal use by 2026. 50 There is heterogeneity in the disease burden, vaccine cost-effectiveness, and programmatic preparedness by region, emphasizing the need for local assessments and decision-making with tiered and fair vaccine pricing.…”