Progress Toward Vaginal GBS Vaccine Is Seen : Colonization by group B streptococci is probably the single most important risk factor for neonatal sepsis.


BOSTON — Women with increased levels of type-specific serum antibody against group B streptococci may be protected from vaginal colonization by those serotypes, a study has shown.

The findings support current efforts to develop a vaccine to decrease vaginal acquisition and fetal transmission of the bacteria, lead investigator Dr. Sharon Hillier said at the annual meeting of the Infectious Diseases Society for Obstetrics and Gynecology.

It has long been recognized that vaginal colonization by group B streptococci (GBS) is probably the single most important risk factor for neonatal sepsis, and while wider use of prophylactic intrapartum antibiotics has led to a substantial decline in the incidence of GBS infection in newborns, “a lot of women do develop amniotic fluid infections, preterm delivery, or even pregnancy loss due to [the bacteria],” said Dr. Hillier of the University of Pittsburgh's Magee-Women's Hospital. “We really haven't understood why women become vaginally colonized with GBS and we have few options for interrupting vaginal colonization. Prophylactic antibiotic treatment has been useful as an interim strategy, but it is just that—an interim strategy.” The longer-term objective, she said, is to develop a vaccine against GBS that will reduce vaginal colonization, prevent transmission to the neonate, and reduce overall morbidity.

The testing of potential vaccines is a logistical challenge, however, “because the incidence of neonatal sepsis is so low,” Dr. Hillier said. “Even if an effective vaccine is developed, it would require more than 100,000 participants to achieve an even modestly powered vaccine trial.”

In an effort to uncover surrogate end points for measuring GBS vaccine efficacy, Dr. Hillier and her colleagues designed the current study to evaluate the impact of naturally acquired antibodies on GBS acquisition, based on data from Haemophilus influenzae type b (Hib) vaccine research demonstrating that the Hib vaccine not only decreases Hib infection, but also reduces nasopharyngeal Hib colonization. As with GBS, a crucial factor in Hib virulence is the production of an antigenically variable polysaccharide capsule, she noted.

To test their hypothesis, the investigators enrolled 1,248 sexually active nonpregnant women aged 18–30 years in the study. At quarterly visits during the course of the study year, serum was collected from each of the women for evaluation of type-specific IgG antibody against the most common GBS serotypes. In addition, vaginal cultures were performed using selective broth medium for GBS; demographic and behavioral information, and vaginal flora assessments were also obtained. Based on the results from 1,089 women who returned for the quarterly visits, 973 women-years of follow-up were collected, said Dr. Hillier.

The median age of the predominantly white (61% vs. 35% black) study population was 21 years. “We specifically targeted younger women because of their higher level of sexual activity and increased incidence of GBS sepsis,” noted Dr. Hillier.

During the evaluation period, the investigators recorded 298 GBS acquisitions, including 111 of serotype Ia, 26 of serotype II, 116 of serotype III, and 45 of serotype V, Dr. Hillier reported. Within and across the serotypes, “there was a strong association between the concentration of humeral antibody and acquisition of GBS,” said Dr. Hillier, noting that overall, 61% of the GBS acquisitions occurred among women with 0.5 mcg/mL or less serum antibody to the respective serotype, while only 5% occurred among women with 3.0–5.0 mcg/mL of serum antibody.

“There was a strong relationship between the concentration of humeral antibody in the visit before the acquisition of GBS and the protective effect against acquisition,” Dr. Hillier explained. “In type Ia, for example, about 50% of the GBS acquisitions occurred in women who had less than 0.5 mcg/mL of humeral antibody against type Ia at the previous visit.” Similar percentages were observed for the other serotypes, she said, noting that the linear association between concentration of antibody and acquisition of GBS was especially robust in serotype III, one of the most common serotypes that colonize women.

The results of an adjusted hazards ratio using a Cox proportional hazards model for vaginal type III GBS acquisition showed a 70% reduction in acquisition of type III GBS among women with high levels of type III antibodies, said Dr. Hillier, noting that the independent association was consistent across multiple models.

“This finding leads us to believe that vaccination to induce high levels of serum antibody to type III GBS may result in decreased vaginal colonization of that serotype,” said Dr. Hillier. To test this, she and her colleagues are conducting a National Institutes of Health-funded phase II randomized, double-blind clinical trial called SPIN (Streptococcal Prevention in Nonpregnant Women) of 50-mcg type III GBS polysaccharide-tetanus toxoid conjugate vaccine.

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