A randomized trial of conjugated group B streptococcal type Ia vaccine in a rabbit model of ascending infection

Maternal vaccination may become a central strategy in the prevention of early-onset group B Streptococcal sepsis. Unlike earlier group B streptococcal polysaccharide vaccines that were poorly immunogenic, newer vaccines conjugated to tetanus toxoid have been developed and have improved immunogenicity. We sought to evaluate a conjugated vaccine using our rabbit model of ascending infection.

Rabbit does were randomized to receive either conjugated group B streptococcal type Ia (Ia-tetanus toxoid) or conjugated group B streptococcal type III (III-tetanus toxoid) vaccine. Does were vaccinated 7 days before conception and 7 and 21 days after conception. On days 28 to 30 of a 30-day gestation, does were inoculated intracervically with 10(6) colony-forming units of type Ia group B Streptococcus. Labor was induced if does were undelivered after 72 hours. Does were observed up to 7 days after inoculation. Offspring were observed up to 4 days. We obtained maternal cultures from the uterus, peritoneum, and blood and offspring cultures from the mouth, anus, and blood. Antibody levels were also determined.

Offspring survival was significantly improved in the group receiving Ia-tetanus toxoid (P =.047). Outcomes such as maternal sepsis and severe illness, although not reaching statistical significance, showed a trend toward improved outcomes in the Ia-tetanus toxoid group.

This is the first study to evaluate the conjugated group B streptococcal vaccine by using any model of ascending infection. The Ia-tetanus toxoid vaccine led to improved survival and was immunogenic but fell short of its expected efficacy in preventing ascending group B streptococcal disease under these experimental conditions.