Phase 1/2 Trial Evaluates Maternal GBS Vaccine for Newborns

Clinical Evaluation and Study Design of GBS6

Stage 1 took place in South Africa involving healthy non-pregnant participants 18 to 40 years of age at enrollment, who received the highest tested GBS6 dose level of 20 µg formulated with and without AlPO₄. Following a protocol amendment, these stage 1 non-pregnant participants could return and re-consent to receive a booster dose of GBS6 with AlPO₄ at the 20-µg dose level approximately two years after their primary dose.

Dose-Finding and Progression to Stage 3

Following a review of 1-month postvaccination safety data from stage 1 non-pregnant participants, maternal dose-finding stage 2 assessed three GBS6 dose levels—5 µg, 10 µg, and 20 µg—with or without AlPO₄. This stage evaluated healthy pregnant participants 18 to 40 years of age at 27 to 36 weeks’ gestation in South Africa.

After reviewing safety and immunogenicity data at delivery and birth from stage 2 maternal participants and their infants, researchers selected the GBS6 20-µg dose level formulated without AlPO₄ for stage 3. In the third stage, healthy pregnant individuals from South Africa, the United States, and the United Kingdom at 24 to 36 weeks’ gestation were enrolled to receive either GBS6 or a placebo.

Global Disease Burden and Prevention Challenges

According to data outlined in Frontiers in Public Health, invasive group B streptococcal disease is the most common perinatally acquired bacterial infection in newborns. Streptococcus agalactiae, or Group B Streptococcus (GBS), is the leading reported cause of early-onset disease in neonates during the first six days after birth. Worldwide, Bayesian modelling estimated 394,000 cases of invasive GBS disease and 58,300 early infancy deaths.

The burden is exceptionally high in African countries where intrapartum antibiotic prophylaxis strategies are unfeasible. Sub-Saharan Africa accounts for 90,800 early-onset disease cases, where almost one in four newborns with early-onset disease will die, and one in ten survivors experience moderate or severe neurodevelopmental impairment. Furthermore, GBS causes substantial in-utero infection burdens, resulting in 20,300 stillbirths out of 46,200 total GBS stillbirths in sub-Saharan Africa in 2020.

Regulatory Pathways and Immunologic Threshold Models

Developing maternal vaccines has faced historical hurdles, including industry reluctance to conduct research on pregnant populations, according to insights reported by Drugdiscoverynews. Rebecca Kahn, an infectious disease epidemiologist and Epidemic Intelligence Service fellow at the Centers for Disease Control and Prevention, noted that GBS causes approximately 90,000 infant deaths and 50,000 stillbirths annually.

To overcome barriers preventing phase 3 trials, the Food and Drug Administration decided that clinical trials could measure whether a maternal vaccine leads to sufficient fetal antibody production to protect against disease, rather than exclusively measuring direct disease prevention. Researchers like Stephanie Schrag and colleagues have worked to determine the necessary immunologic correlate threshold using data from observational studies.