2023-08-15 15:12:15
Why is this important?
Group B streptococcus is a common cause of sepsis and meningitis in newborns and infants up to 3 months of age. The main risk factor for this disease is the exposure of the newborn to maternal rectovaginal colonization by group B streptococci during childbirth. Ascending group B streptococcal infection in the mother can also affect the fetus before delivery, resulting in intra-amniotic infection, premature labor, or stillbirth.
In many high-income countries, pregnant women are screened at the end of the 3rd trimester of pregnancy and antibiotic prophylaxis is administered if positive. This is more than 80% effective in countering the early onset of the disease in infants (0 to 6 days of life), but is not effective against the late onset of the disease (between 7 and 89 days of life) or the prenatal sequelae associated with the infection.
Group B streptococcus expresses capsular polysaccharides (CPS) which are important virulence factors. Of the 10 defined serotypes, 6 have been associated with 98% of cases of invasive disease in infants worldwide. This hexavalent glycoconjugate vaccine against the capsular polysaccharide (GBS6) could therefore reduce the risk of disease in infants and the use of antibiotic therapy for prophylaxis, which is not without risk in terms of antibiotic resistance and disruption of the microbiome of the child.
Methodology
A phase 2, controlled study versus placebo, evaluated the immunogenicity and safety of different GBS6 vaccine formulations, and a seroepidemiological study evaluated the concentrations of anti-CPS specific IgG acquired naturally by the newborn and associated with a possible reduction in the risk of disease invasive up to 89 days of age. The aim was to establish a putative protective threshold. The safety and immunogenicity of a single dose of various formulations of GBS6 were assessed as well as maternally transmitted anti-CPS antibodies.
Principle results
Overall, 17,752 pregnant women benefited from prospective screening and were included in the study. Rectal and vaginal swabs taken at the time of delivery from a selected subgroup of 2,950 women showed that approximately 26% were carriers of group B streptococcus. Among the neonates, 28 cases of invasive streptococcal disease were recorded within 89 days of life. The overall incidence was 0.72 cases/1000 live births for early onset infection and 0.83/1000 live births for late onset disease. The naturally acquired anti-CPS IgG concentrations associated with a 75-95% reduction in the risk of invasive disease in infants were 0.184-0.827 μg per milliliter.
No safety signal was observed in mothers and infants following injection of GBS6. Local reactions were generally mild to moderate, and pain at the injection site was more often reported in those who received GBS6 with aluminum phosphate. Systemic events were similar in the GBS6 and placebo groups, and most were mild to moderate in intensity. In infants, the most frequent serious adverse events were minor congenital anomalies (umbilical hernia, congenital cutaneous melanocytosis).
GBS6 induced maternal antibody responses to all serotypes, with a mother-infant antibody ratio of approximately 0.4 to 1.3 depending on the dose used.
Only one stillbirth occurred in a GSB6 recipient, and was not considered vaccine-related. The percentage of infants with anti-CPS IgG concentrations greater than 0.184 μg per milliliter varied by serotype and formulation, and 57–97% of infants had a serological response to the most immunogenic formulation.
Principales limitations
This study was conducted in South Africa, a low- and middle-income region with high endemicity of group B streptococcal disease and where microbiological screening and antibiotic prophylaxis is not the standard of care. It will be useful to confirm these data on higher income populations.
Funding
Study funded by the Pfizer laboratory and the Bill and Melinda Gates Foundation.
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