A Phase 2, Randomized, Control Trial of Group B Streptococcus (GBS) Type III Capsular Polysaccharide-tetanus Toxoid (GBS III-TT) Vaccine to Prevent Vaginal Colonization with GBS III

Sharon L. Hillier, Patricia Ferrieri, Morven S. Edwards, Marian Ewell, Daron Ferris, Paul Fine, Vincent Carey, Leslie Meyn, Dakota Hoagland, Dennis L. Kasper, Lawrence C. Paoletti, Heather Hill, Carol J. Baker

Research output: Contribution to journalArticlepeer-review

5 Scopus citations

Abstract

Background: Group B Streptococcus (GBS) frequently colonizes pregnant women and can cause sepsis and meningitis in young infants. If colonization was prevented through maternal immunization, a reduction in perinatal GBS disease might be possible. A GBS type III capsular polysaccharide (CPS)-tetanus toxoid conjugate (III-TT) vaccine was evaluated for safety and efficacy in preventing acquisition of GBS colonization. Methods: Healthy, nonpregnant women aged 18-40 years and screened to be GBS III vaginal and rectal culture negative were randomized to receive III-TT conjugate or tetanus diphtheria toxoid vaccine in a multicenter, observer-blinded trial. GBS vaginal and rectal cultures and blood were obtained bimonthly over 18 months. Serum concentrations of GBS III CPS-specific antibodies were determined using enzyme-linked immunosorbent assay. Results: Among 1525 women screened, 650 were eligible for the intent-to-treat analysis. For time to first acquisition of vaginal GBS III, vaccine efficacy was 36% (95% confidence interval [CI], 1%-58%; P =. 044), and for first rectal acquisition efficacy was 43% (95% CI, 11% to 63%; P =. 014). Two months post-immunization, geometric mean concentrations of serum GBS type III CPS-specific immunoglobulin G were 12.6 μg/mL (95% CI, 9.95 to 15.81) in GBS III-TT recipients, representing a 4-fold increase from baseline in 95% of women, which persisted. Both vaccines were well tolerated. Conclusions: GBS CPS III-TT conjugate vaccine significantly delayed acquisition of vaginal and rectal GBS III colonization. In addition to its use for maternal immunization to passively protect infants with maternally derived antibodies, a multivalent vaccine might also serve to reduce fetal and neonatal exposure to GBS. Clinical Trials Registration: NCT00128219.

Original languageEnglish (US)
Article numberciy838
Pages (from-to)2079-2086
Number of pages8
JournalClinical Infectious Diseases
Volume68
Issue number12
DOIs
StatePublished - Jun 2019

Bibliographical note

Funding Information:
Financial support. This work was supported by the National Institute of Allergy and Infectious Diseases at the National Institutes of Health (NIH; N01-AI-25495).

Funding Information:
Potential conflicts of interest. M. S. E. reports receiving grant funding from Pfizer, Inc. S. L. H. reports grants from the NIH during the conduct of the study and personal fees from Merck and grants from Cepheid outside the submitted work. M. E. reports another NIH contract (HHSN272201500002C)

Funding Information:
during the conduct of the study. P. F. reports grants from the NIH during the conduct of the study. C. J. B. reports grants from the NIH during the conduct of the study. D. L. K. reports grants from the NIH during the conduct of the study. H. H. was a contract employee for the Emmes Corporation during the conduct of the study. L. C. P. reports grants from the NIH during the conduct of the study. All other authors report no potential conflicts. All authors have submitted the ICMJE Form for Disclosure of Potential Conflicts of Interest. Conflicts that the editors consider relevant to the content of the manuscript have been disclosed.

Keywords

  • GBS
  • rectal colonization
  • vaccine
  • vaginal colonization

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