Prevention of GBS Colonization Via Immunity
Condition: Beta Haemolytic Streptococcal Infection
MeSH terms: Streptococcal Infections
Study type: Interventional
Phase: Phase 2

Summary: 
      The group B streptococcus (GBS) vaccine study is being done to see if a single vaccination
      with a GBS type III vaccine can stop women from getting GBS type III bacteria in the vagina.
      Approximately 600 women, ages 18-40, will be enrolled from the clinical sites participating
      in this study. Participants will be non-pregnant, sexually active (sex with a male at least
      once in the last 4 months), and GBS negative in the vagina or rectum at the screening visit.
      Participants will be randomly assigned to receive the experimental GBS type III vaccine or a
      licensed vaccine containing Tetanus and Diphtheria Toxoids (Td). Participants will be
      followed at one month, 2 months and every other month thereafter following vaccination (for
      vaginal and rectal swab collection and a blood draw) for 1½ years or a total of 10 post
      vaccination visits.
    

Detailed description: 
      Vaginal colonization is the single most important risk factor for transmission of group B
      Streptococcus (GBS) from mothers to neonates, resulting in neonatal sepsis and/or meningitis.
      The long-term goal of this study is to determine whether vaccine-induced serum antibody to
      type III GBS will be sufficient to prevent vaginal acquisition of type III GBS. This study is
      linked to Division of Microbiology and Infectious Diseases protocol 04-018. It is a
      randomized, double-blinded, comparative clinical trial among young (18-40 years old),
      non-pregnant, sexually active women who are not currently colonized vaginally or rectally
      with type III GBS, it will be conducted to evaluate the efficacy of a GBS type III-TT vaccine
      for prevention of type III GBS vaginal acquisition. The observation period for each patient
      will be 18 months following vaccination. The specific objectives are: enroll 600 women
      (previously screened within last 14 days in a GBS Screening Protocol) identified as GBS type
      III negative, vaginally and rectally; vaccinate 600 women randomized to a 1:1 ratio with 50
      micrograms of type III GBS polysaccharide conjugated to tetanus toxoid (GBS III-TT) or
      licensed vaccine containing Tetanus and Diphtheria Toxoids adsorbed for adult use (Td);
      measure reactogenicity by subject report in a 7-day symptom diary and by 1-2 day follow-up
      telephone call; evaluate women at 1, 2, 4, 6, 8, 10, 12, 14, 16 and 18 months for serum
      antibody response. Blood will be obtained at each of these clinic follow-up visits and serum
      will be used to compare type III GBS specific antibody levels at baseline and follow-up;
      assess vaginal and rectal acquisition by GBS at months 1, 2, 4, 6, 8, 10, 12, 14, 16 and 18
      months using specimens obtained at the clinic visits; compare women receiving GBS III-TT
      vaccine to women receiving Td vaccine with respect to the time to first vaginal culture
      positive for type III GBS; assess the relationship between person-level covariates, including
      features of the decrease of type III GBS antibody levels over time, and the time to first
      vaginal culture positive for type III GBS; and assess the effect of vaginal colonization by
      hydrogen peroxide (H2O2)-producing Lactobacillus, sexual activity, antibiotic usage, rectal
      colonization with GBS and demographic features as risk factors for acquisition of type III
      GBS, independent of serum antibody levels. The primary study endpoint will be the time to the
      first vaginal swab that is type III GBS culture positive, with all previous cultures negative
      for type III GBS, not just the immediately preceding culture. The secondary endpoints
      include: the proportion of vaginal swabs that are type III GBS culture positive; the
      proportion of subjects whose vaginal cultures are type III GBS culture negative throughout
      the study; the frequency of vaginal colonization with GBS serotypes Ia, Ib, II and V; the
      measurement of serum immunoglobulin (Ig)G antibody levels to type III GBS at 1, 2, 4, 6, 8,
      10 12, 14, 16 and 18 months following vaccination; the measurement of post-vaccination
      antibody levels to type III GBS, stratified by pre-vaccination levels of native antibody; the
      frequency of local and systemic symptoms attributable to vaccination; and the density of type
      III GBS cultured from vaginal swabs at culture positive visits.
    

Intervention name(s): GBS III-TT; Tetanus and diptheria toxoids vaccine
Intervention type(s): Biological; Biological
Intervention description(s): 50 mcg GBS Type III capsular polysaccharide conjugated to 32 mcg of tetanus toxoid. A single dose of vaccine administered by intramuscular (IM) injection in the upper arm. All subjects will receive a volume of 0.5 ml.; Td vaccine is a sterile solution of alum-precipitated toxoids in isotonic sodium chloride solution. A single dose of vaccine will be administered by intramuscular (IM) injection in the upper arm. All subjects will receive a volume of 0.5 ml. Each 0.5 ml dose is formulated to contain 5 Lf (flocculation units) of tetanus toxoid and 2 Lf of diphtheria toxoid.
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: Double (Participant, Investigator)
Primary purpose: Prevention
Keywords: Group B Streptococcus, women, vaccine