Maternal group B strep vaccine shows promise in phase 2 trial

Key takeaways:

• Pregnant women who received Pfizer’s group B streptococcus vaccine transferred antibodies to their infants.
• The phase 2 trial uncovered no safety concerns related to receiving the vaccine.

Pregnant women who received an investigational group B streptococcus vaccine in a phase 2 trial transferred antibodies to their infants “at levels associated with a reduced risk of invasive group B streptococcal disease,” researchers found.

The trial found no safety signals associated with receiving the vaccine, according to findings published Wednesday in The New England Journal of Medicine.

Group B streptococcus (GBS) bacteria are common and usually not harmful, although GBS infection can cause serious illness, especially in newborns, according to the CDC. GBS is known to cause many stillbirths and infant deaths.

Pfizer’s GBS vaccine, a hexavalent vaccine known as GBS6, received breakthrough therapy designation from the FDA last fall.

“In the United States and many other high-income countries, pregnant women undergo screening for group B streptococcal colonization late in the third trimester, and intrapartum antibiotic prophylaxis is administered to those with positive results,” the authors of the new study wrote.

“Intrapartum antibiotic prophylaxis is more than 80% effective in the prevention of early-onset disease in infants (at 0 to 6 days of age) but has not been effective against late-onset disease (at 7 to 89 days) or prebirth sequelae associated with group B streptococcal infection,” they wrote.

The researchers conducted a phase 2 trial of the vaccine in South Africa that enrolled and monitored mother-infant pairs for the development of invasive GBS disease in the infant through 89 days. Following a screening, they assigned 360 mothers to receive either a single dose of 5 g, 10 g or 20 g per serotype of GBS6 with or without aluminum phosphate, or a placebo.

Severe systemic events were reported in four GBS6 recipients and four placebo recipients, with unsolicited adverse events occurring in 45% to 70% of the participants in the GBS6 groups and in 61% of those in the placebo group, according to the researchers. There were three infant deaths, including one in the study group, but all three were deemed unrelated to the trial or the placebo, the researchers said.

In terms of protection, “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 researchers wrote. “The percentage of infants with anti-CPS IgG concentrations above 0.184 g per milliliter varied according to serotype and formulation, with 57[%] to 97% of the infants having a seroresponse to the most immunogenic formulation.”

“In this initial assessment of the GBS6 vaccine in pregnant women, no safety concerns associated with GBS6 were identified, and IgG responses to all six serotypes were elicited, which were sustained through delivery and transferred to infants,” they wrote.

In an accompanying editorial, Carol J. Baker, MD, professor of pediatrics at McGovern Medical School at the University of Texas Health Science Center, noted that “no one involved in the care of pregnant women or young infants would question the impact of group B streptococcus as a cause of disease, disability, and death.”

“With the recognition of group B streptococcus as a growing public health problem, the Centers for Disease Control and Prevention, while awaiting the development of a maternal vaccine, initiated active surveillance for invasive disease and, in 1996, published the first of several subsequent ‘interim’ group B streptococcus prevention guidelines,” Baker wrote.

“By 2005, this policy was associated with a reduction of more than 80% in the incidence of early-onset disease,” Baker continued. “This level of effectiveness continues today, and the policy has been adopted by several European countries. Although this public health victory is an important step forward, it addresses only one portion of the continuing perinatal disease burden of group B streptococcus-associated stillbirths in the third trimester, maternal invasive infections (including sepsis), residual early-onset cases, and all late-onset infant disease.”

The findings would be “historic,” Baker said.

“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,” Baker wrote.

References:

Baker CJ, et al. N Engl J Med. 2023;doi: 10.1056/NEJMe2306234.

Madhi SA, et al. N Engl J Med. 2023;doi:10.1056/NEJMoa2116045.

FDA grants breakthrough therapy designation to Pfizer’s group B streptococcus vaccine candidate to help prevent infection in infants via immunization of pregnant women. https://www.pfizer.com/news/press-release/press-release-detail/fda-grants-breakthrough-therapy-designation-pfizers-group-b. Published Sept. 7, 2022. Accessed Jan. 19, 2023.