A hexavalent anti–capsular polysaccharide (CPS)–cross-reactive material 197 glycoconjugate vaccine (GBS6) was immunogenic and resulted in the transfer of protective antibodies to young infants at levels associated with a reduced risk of invasive group B streptococcal disease, researchers report. The product is being developed as a maternal vaccine administered during pregnancy to provide protection to infants after birth.
In the ongoing phase 2, placebo-controlled trial, the safety and immunogenicity of a single dose of various GBS6 formulations were analyzed based on the maternal transfer of anti-CPS antibodies. A parallel seroepidemiologic study conducted in the same population looked at the serotype-specific anti-CPS IgG concentrations associated with a reduced risk of invasive disease among newborns through 89 days of age.
“Naturally acquired anti-CPS IgG concentrations were associated with a reduced risk of disease among infants in the seroepidemiologic study,” the authors write. “IgG thresholds that were determined to be associated with 75 to 95% reductions in the risk of disease were 0.184 to 0.827 μg per milliliter. No GBS6-associated safety signals were observed among the mothers or infants. The incidence of adverse events and of serious adverse events were similar across the trial groups for both mothers and infants; more local reactions were observed in the groups that received GBS6 containing aluminum phosphate. Among the infants, the most common serious adverse events were minor congenital anomalies (umbilical hernia and congenital dermal melanocytosis). GBS6 induced maternal antibody responses to all serotypes, with maternal-to-infant antibody ratios of approximately 0.4 to 1.3, depending on the dose. The percentage of infants with anti-CPS IgG concentrations above 0.184 μg per milliliter varied according to serotype and formulation, with 57 to 97% of the infants having a seroresponse to the most immunogenic formulation.”
Editorial: “The identification of a single set of protective antibody concentrations across multiple group B streptococcal capsular types mimics the historic achievement for Streptococcus pneumoniae conjugate vaccines after the completion of phase 3 efficacy trials, licensure from the Food and Drug Administration, and widespread use,” writes an editorialist. “Although the results of the investigations by Madhi et al. provide a framework into which a future correlate of protection for group B streptococcus may be viewed, there are some limitations. The results were derived from a single study in which only 17% had group B streptococcal disease due to four of the six CPS serotypes in the vaccine; they were obtained with a limited number of matched infant controls to case patients (e.g., 0.63:1 in prospective study); they apply only to a South African pregnant population with a high disease burden among infants; and they require corroboration in future studies. However, the road to group B streptococcal vaccine licensure could occur through an accelerated pathway based on an established serologic correlate of protection followed by confirmation of effectiveness. The authors take a novel and valuable step toward the goal of victory over the global public health challenge of group B streptococcal perinatal disease by keeping Sisyphus’ boulder atop the mountain.”