Group B streptococcus is the most common cause of early- and late-onset neonatal sepsis.
Flor Munoz, MD, MSc, associate professor of pediatrics at Baylor College of Medicine, provided an update on maternal Group B Streptococcus (GBS) vaccines at IDWeek 2023.1
GBS is the most common cause of early and late-onset neonatal sepsis. But perhaps less well-recognized is that GBS is also an important cause of maternal infection, stillbirths, preterm births, neonatal death, and neurodevelopmental impairment. While intrapartum antibiotic prophylaxis has led to a decrease in early-onset sepsis, it has no effect on late-onset sepsis or the aforementioned sequelae of infection. A high proportion of the disease burden is in low-income and middle-income countries where intrapartum antibiotic prophylaxis is more challenging to implement. Maternal immunization would be a strategy to reduce GBS-related morbidity and mortality more broadly.
Research towards a safe, effective, and acceptable vaccine to prevent neonatal GBS disease has been ongoing for sixty years, with several clinical trials of GBS vaccines in pregnant persons having been carried out in the 1980s and 1990s. The World Health Organization published a GBS vaccine development technology roadmap in 2017 outlining the strategic goals of vaccine development.
Munoz highlights several sentinel publications in recent years demonstrating progress in the road toward GBS vaccine and shedding light on key questions necessary to know to develop an effective GBS vaccine: What are the correlates of protection against the major GBS disease-causing serotypes in infants? What level of antibody is needed to protect infants?
Munoz highlights promising findings from 2 phase 2 clinical trials. The first is a hexavalent capsular polysaccharide (CPS) conjugate of the GBS6 vaccine. It contains 6 serotypes (Ia, Ib, II, III, IV, and V) that are most prevalent and cause 98% of disease. The phase 2 trial has shown that GBS6 was well tolerated and induced maternal antibody response to all serotypes. These results will inform a planned phase 3 clinical development program. The second candidate is an adjuvant protein-only vaccine, based on the N-termini domains of the most prevalent alpha-like protein serotypes, overall covering close to 100% of clinical GBS.
Addressing concentration, a study published this year in the New England Journal of Medicine evaluated which concentrations of transplacentally transferred IgG would be necessary to reduce disease in infants. Investigators determined a threshold of antibody concentration (0.8 micrograms/L) that would achieve 75% to 95% reduction in disease in infants.2
Munoz conveys optimism based on substantial progress made in the past several years on case definition, standardization of lab assays, and an understanding of correlates of protection, transplancental antibody transfer, as well as progression toward evaluating candidate vaccines in pregnant participants in pivotal phase 3 studies.
Moving forward, Munoz stressed the importance of well-established and reliable disease diagnosis and surveillance systems in place to ascertain safety and impact of maternal vaccinations against GBS.