Preclinical evaluation of group B streptococcal polysaccharide conjugate vaccines prepared with a modified diphtheria toxin and a recombinant duck hepatitis B core antigen

An effective vaccine against group B streptococcal (GBS) disease will undou btedly include capsular polysaccharides (CPSs) from each of the five seroty pes prevalent in the United States individually coupled to immunogenic prot eins. 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 c ore antigen (rdHBcAg), a particulate protein of viral origin, and a newly m utated 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-rdHBc Ag 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 sur vivors 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 fr om dams correlated with pup survival in groups that received a conjugate va ccine, and this serum was opsonically active in vitro against GBS type Ill. In addition. carrier-specific IgG was also measured in ser-um from vaccina ted mice. These data suggest that the rdHBcAg and DTm may be effective carr iers for GBS CPSs. (C) 2001 Elsevier Science Ltd. All rights reserved.