title: Preclinical evaluation of group B streptococcal polysaccharide conjugate vaccines prepared with a modified diphtheria toxin and a recombinant duck hepatitis B core antigen.
abstract: An effective vaccine against group B streptococcal (GBS) disease will undoubtedly include capsular polysaccharides (CPSs) from each of the five serotypes prevalent in the United States individually coupled to immunogenic proteins. This formulation may require the use of two or more different protein carriers. We preclinically examined the potential of two proteins to serve as effective carriers for GBS type III CPS. Recombinant duck hepatitis B core antigen (rdHBcAg), a particulate protein of viral origin, and a newly mutated form of diphtheria toxin (DTm) were covalently and directly coupled to purified type III CPS by reductive amination. Seventy-seven of 79 (97%) newborn pups born to mouse dams actively vaccinated with type III CPS-rdHBcAg conjugate survived GBS type III challenge, whereas none of the pups born to dams that received an uncoupled mixture of type III CPS and rdHBcAg or saline survived. Likewise, 64 (98%) of 65 pups born to dams vaccinated with type III CPS-DTm conjugate survived challenge, in sharp contrast to no survivors among the pups born to dams vaccinated with an uncoupled mixture of type III CPS and DTm. The presence of type III CPS-specific IgG in serum from dams correlated with pup survival in groups that received a conjugate vaccine, and this serum was opsonically active in vitro against GBS type III. In addition, carrier-specific IgG was also measured in serum from vaccinated mice. These data suggest that the rdHBcAg and DTm may be effective carriers for GBS CPSs.
authors.affiliation: Channing Laboratory, Department of Medicine, Brigham and Women's Hospital, 181 Longwood Avenue, Boston, MA 02115, USA. lpaoletti@channing.harvard.edu
authors.forename: L C
authors.initials: LC
authors.lastname: Paoletti
authors.forename: D L
authors.initials: DL
authors.lastname: Peterson
authors.forename: R
authors.initials: R
authors.lastname: Legmann
authors.forename: R J
authors.initials: RJ
authors.lastname: Collier
mesh_terms: D000818:Animals; D016667:Bacterial Capsules / Q000276:immunology*; D004167:Diphtheria Toxin / Q000008:administration & dosage / Q000276:immunology*; D005260:Female; D006512:Hepatitis B Core Antigens / Q000276:immunology*; D015611:Hepatitis B Virus, Duck / Q000276:immunology*; D007106:Immune Sera / Q000276:immunology; D051379:Mice; D011994:Recombinant Proteins / Q000276:immunology; D022541:Streptococcal Vaccines / Q000008:administration & dosage / Q000276:immunology*; D013292:Streptococcus agalactiae / Q000276:immunology*; D014614:Vaccines, Synthetic / Q000276:immunology*
chemical_list: D004167:Diphtheria Toxin; D006512:Hepatitis B Core Antigens; D007106:Immune Sera; D011994:Recombinant Proteins; D022541:Streptococcal Vaccines; D014614:Vaccines, Synthetic