Neonatal mouse protection against infection with multiple group B streptococcal (GBS) serotypes by maternal immunization with a tetravalent GBS polysaccharide-tetanus toxoid conjugate vaccine

Paoletti, Lawrence C.; Wessels, Michael R.; Rodewald, A K; Shroff, Ankit; Jennings, Harold J.; Kasper, Dennis L.

doi:10.1128/iai.62.8.3236-3243.1994

Cited by 88 publications

(29 citation statements)

References 35 publications

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“…A recent publication demonstrates induction of protective antibodies against S. parasanguis endocarditis in an animal model after vaccination with recombinant FimA (37). Current vaccine approaches for GBS favor the use of proteins linked to polysaccharide structures of the capsule (15,20,25,26). None of the presently identified surface proteins of GBS are found in every known serotype; given the presence of Lmb in all of these serotypes, the protein may be a good candidate for GBS vaccine.…”

Section: Discussionmentioning

confidence: 99%

Lmb, a Protein with Similarities to the LraI Adhesin Family, Mediates Attachment of Streptococcus agalactiae to Human Laminin

Rozdzinski²,

et al. 1999

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Streptococcus agalactiae is a leading cause of neonatal sepsis and meningitis. Adherence to extracellular matrix proteins is considered an important factor in the pathogenesis of infection, but the genetic determinants of this process remain largely unknown. We identified and sequenced a gene which codes for a putative lipoprotein that exhibits significant homology to the streptococcal LraI protein family. Mutants of this locus were demonstrated to have substantially reduced adherence to immobilized human laminin. The nucleotide sequence of the gene was subsequently designated lmb (laminin binding) and shown to be present in all of the common serotypes of S. agalactiae. To determine the role of Lmb in the adhesion of S. agalactiaewild-type strains to laminin, a recombinant Lmb protein harboring six consecutive histidine residues at the C terminus was cloned, expressed, and purified from Escherichia coli. Preincubation of immobilized laminin with recombinant Lmb significantly reduced adherence of the wild-type strain O90R to laminin. These results indicate that Lmb mediates the attachment of S. agalactiae to human laminin, which may be essential for the bacterial colonization of damaged epithelium and translocation of bacteria into the bloodstream.

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Section: Discussionmentioning

confidence: 99%

Lmb, a Protein with Similarities to the LraI Adhesin Family, Mediates Attachment of Streptococcus agalactiae to Human Laminin

Rozdzinski²,

et al. 1999

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“…By coupling the PS covalently to a protein carrier, such as tetanus or diphtheria toxoid, they can be converted to T-cell-dependent antigens, which results in an increase in the immunogenicity and a memory antibody response (3). This has been done successfully with several PS such as H. influenzae type b CPS (36), group B streptococcus CPS (26,31), Streptococcus pneumoniae CPS (13), Staphylococcus aureus type 5 and 8 CPS (12), and Salmonella typhi Vi PS (46), although as yet H. influenzae type b CPS is the only PS used in a conjugate vaccine licensed for human use. All these vaccines and vaccine candidates are designed for systemic administration.…”

mentioning

confidence: 99%

Local and systemic antibody responses to dextran-cholera toxin B subunit conjugates

et al. 1995

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This study was designed to test local and systemic immunity following mucosal immunization with a polysaccharide-protein conjugate. After preparing and characterizing dextran-cholera toxin B subunit (CTB) conjugates, we studied their immunogenicity in mice following systemic or mucosal immunizations. Dextran was chosen as a model polysaccharide antigen and conjugated via adipic acid dihydrazide and N-succinimidyl-3-(2-pyridyldithio)propionate to CTB. Mice were immunized either subcutaneously, intranasally, or perorally three times, and cholera toxin was used as an adjuvant for the mucosal immunizations. Three conjugates with different molecular weights for dextran (40,000 and 76,000) or varying dextran/CTB molar ratios were tested. Peroral immunizations with all conjugates evoked local immunoglobulin A (IgA) antibody responses against dextran in the small intestine, and intranasal immunizations did the same in the lung. Intranasal immunizations also elicited serum antibody titers that were significantly higher than or equal to those after subcutaneous immunizations. Intranasal immunizations evoked serum IgG antidextran titers which were dependent on the dextran/CTB molar ratio and inversely related to the local IgA response, which was not the case for subcutaneous immunizations. This is the first study of local and systemic immunity following mucosal immunization with a polysaccharide-protein conjugate. The results show that it is possible to evoke a local as well as a systemic antibody response against a polysaccharide by conjugating it to CTB and using an appropriate route of immunization.

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“…Cells removed from the chemostat were washed, and cell walls were digested with mutanolysin as described previously (27). Inhibition enzyme-linked immunosorbent assay was used to quantify the amount of each cell component as previously described (27), with the following reagents: for cell-associated CPS types Ia, Ib, and III, homologous serotype-specific rabbit antiserum (diluted 1:100,000) (26,35,36), purified homologous CPS as the standard, and homologous CPS coupled to poly-L-lysine as the coating antigen; for group B antigen, rabbit serum (diluted 1:100,000) raised to group B antigen coupled to tetanus toxoid (19), purified group B antigen as the standard, and group B antigen coupled to human serum albumin as the coating antigen; for alpha and beta C proteins, mouse antiserum raised to alpha (diluted 1:1,000) and rabbit antiserum raised to beta (diluted 1:50,000), and purified antigens as the standards and coating antigens.…”

Section: Methodsmentioning

confidence: 99%

Regulation of Cell Component Production by Growth Rate in the Group BStreptococcus

Ross¹,

Madoff

Paoletti³

1999

J Bacteriol

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Group B Streptococcus (GBS) is the leading cause of bacterial sepsis and meningitis among neonates. While the capsular polysaccharide (CPS) is an important virulence factor of GBS, other cell surface components, such as C proteins, may also play a role in GBS disease. CPS production by GBS type III strain M781 was greater when cells were held at a fast (1.4-h mass-doubling time [td ]) than at a slow (11-htd ) rate of growth. To further investigate growth rate regulation of CPS production and to investigate production of other cell components, different serotypes and strains of GBS were grown in continuous culture in a semidefined and a complex medium. Samples were obtained after at least five generations at the selected growth rate. Cells and cell-free supernatants were processed immediately, and results from all assays were normalized for cell dry weight. All serotypes (Ia, Ib, and III) and strains (one or two strains per serotype) tested produced at least 3.6-fold more CPS at atd of 1.4 h than at atd of 11 h. Production of beta C protein by GBS type Ia strain A909 and type Ib strain H36B was also shown to increase at least 5.5-fold with increased growth rate (production at atd of 1.4 h versus 11 h). The production of alpha C protein by the same strains did not significantly change with increased growth rate. The effect of growth rate on other cell components was also investigated. Production of group B antigen did not change with growth rate, while alkaline phosphatase decreased with increased growth rate. Both CAMP factor and beta-hemolysin production increased fourfold with increased growth rate. Growth rate regulation is specific for select cell components in GBS, including beta C protein, alkaline phosphatase, beta-hemolysin, and CPS production.

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Neonatal mouse protection against infection with multiple group B streptococcal (GBS) serotypes by maternal immunization with a tetravalent GBS polysaccharide-tetanus toxoid conjugate vaccine

Cited by 88 publications

References 35 publications

Lmb, a Protein with Similarities to the LraI Adhesin Family, Mediates Attachment of Streptococcus agalactiae to Human Laminin

Lmb, a Protein with Similarities to the LraI Adhesin Family, Mediates Attachment of Streptococcus agalactiae to Human Laminin

Local and systemic antibody responses to dextran-cholera toxin B subunit conjugates

Regulation of Cell Component Production by Growth Rate in the Group BStreptococcus

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