Synthesis and Preclinical Evaluation of Glycoconjugate Vaccines against Group B Streptococcus Types VI and VIII

Harvard University, Cambridge, Massachusetts, United States
The Journal of Infectious Diseases (Impact Factor: 6). 10/1999; 180(3):892-5. DOI: 10.1086/314955
Source: PubMed


Group B Streptococcus (GBS) types VI and VIII are prevalent among serotypes isolated from pregnant women in Japan. Maternal vaccination with a safe and effective GBS vaccine has been proposed as a rational approach to prevent neonatal GBS disease. Because antibody specific for the capsular polysaccharide (CPS) antigens of GBS is protective, vaccines were developed with purified type VI and VIII CPS coupled to tetanus toxoid. In rabbits the newly synthesized conjugate vaccines elicited high-titered, type-specific antibody that was opsonically active in vitro. Moreover, litters born to mice actively vaccinated with the conjugate vaccines, in contrast to uncoupled CPS or saline, were protected against an ordinarily lethal challenge of GBS of homologous serotype. GBS types VI and VIII conjugate vaccines of the design presented may be important components of a multivalent GBS vaccine for use in regions where these serotypes predominate.

Full-text preview

Available from:
  • Source
    • "However, GBS is also the major cause of bacterial sepsis and meningitis in neonates and a signi¢cant threat of endocarditis and fever in parturient women [1]. A variety of studies have addressed the importance of the capsule for the virulence of GBS and as target for vaccination [2] [13] [22] [23] [27]. Recently, the genomic sequences of the serotype III GBS strain NEM316 [8] and of the serotype V strain 2603 V/R [30] were published, resulting in the identi¢cation of several putative virulence factors from these bacteria. "
    [Show abstract] [Hide abstract]
    ABSTRACT: Group B streptococcus (GBS) is the major cause of bacterial sepsis and meningitis in neonates and poses a significant threat to parturient women. Recently, we identified in GBS the polypeptide PcsB, which is a protein required for cell separation of GBS, and which is also involved in the antibiotic sensitivity of these bacteria. In the present study, the introduction of the pcsB-carrying plasmid pATpcsB into the PcsB-deficient GBS mutant Sep1 restored the phenotype and the antibiotic susceptibility of this strain to that of the GBS wild-type. Although Northern blots revealed a four- to five-fold increased transcription of pcsB in pATpcsB-carrying GBS strains, overexpression of pcsB did not result in higher amounts of PcsB in the cell wall and in the culture supernatant of GBS, indicating regulatory mechanisms that control the translation or secretion of PcsB in these bacteria. In the culture supernatant of mutant Sep1 significant amounts of enolase were identified. As this protein was also present in extracts of cell wall-bound proteins from the GBS wild-type, it can be speculated that GBS can translocate enolase across the cytoplasmic membrane. Northern blot analysis exhibited similar expression of the enolase gene in the GBS strains 6313 and Sep1, indicating that mutant Sep1 is impaired in the anchoring of this protein to its cell wall.
    FEMS Microbiology Letters 05/2003; 221(1):73-9. DOI:10.1016/S0378-1097(03)00167-8 · 2.12 Impact Factor
  • Source

  • Source
    [Show abstract] [Hide abstract]
    ABSTRACT: Maternal colonization with group B Streptococcus (GBS) is a risk factor for neonatal GBS disease. Whereas serotypes Ia, Ib, II, III, and V are prevalent in the United States, types VI and VIII predominate in Japan. Recently, a serotype VIII strain was detected among 114 clinical GBS isolates from a Boston, Mass., hospital.
    Journal of Clinical Microbiology 12/1999; 37(11):3759-60. · 3.99 Impact Factor
Show more