Immunodeterminant specificity of human immunity to type III group B streptococcus.

Abstract

The type III polysaccharides of group B Streptococcus in its native state chemically consists of glucose, galactose, glucosamine, and sialic acid. The core of this polysaccharide lacks sialic acid and precipitates with type III antiserum to give a partial identity with the precipitate between the native antigen and this serum. The core determinant is immunochemically similar to the capsular polysaccharide of type XIV Streptococcus pneumoniae, while the native type III group B streptococcal polysaccharide does not cross-react with type XIV pneumococcal antiserum. In human sera, it is antibody directed to the native antigen which correlates very highly with opsonic immunity (r = 0.94) while a poorer correlation exists between antibody to the core antigen and opsonins (r = 0.51 P less than 0.001). In natural infections, as association exists between low levels of maternal antibody to the native antigen and risk of disease in the infant. This association is not true for antibody to the core structure, where both infected infants and their mothers have much higher levels of antibody to the core than the native antigens. Infected infants are also more likely to respond to infection by developing antibody to the native antigen. Immunization of 12 adults with multivalent pneumococcal polysaccharide induced significantly better antibody response to the core antigen than to the native, and this vaccine induced opsonic activity in only one recipient. Immunization of adults with type III group B streptococcal antigens induced antibody to the native determinant which correlated with opsonic activity. Therefore, it would appear that native group B streptococcal polysaccharides will provide the best candidate antigens for immunization.

Antibody-independent Classical Pathway-mediated Opsonophagocytosis of Type Ia, Group B Streptococcus

“…Although type III strains were not lethal in this standard animal model, type III-specific protective immunity has now been established in models for lethal infection in mice (23)(24)(25), chick embryos (9,26), and suckling rats (27 (1,3,8,9,16). This presumably "protective" antibody has specificity for the native III polysaccharide (2,5), is an IgG immunoglobulin (1,8,9), and is placentally transferred in concentrations that, beyond 35-36 wk of gestation, approach that in maternal serum (1,9). In addition, it promotes opsonophagocytosis and killing of type III strains by polymorphonuclear leukocytes in the presence of complement (4,18), is protective in animal models when sufficient concentrations are administered before or concomitant with challenge (9,25,26), and can modify the terminal sialic acid moieties of the type III capsule in a manner that permits activation of the alternative pathway (4).…”

Structure of the capsular polysaccharide antigen of type IV group B Streptococcus

“…In contrast, it would appear that the type IV polysaccharide (17) resembles more that of type Ib (7,8) in which this conformational dependence was not detected.…”

“…While still retaining type-specificity, these acid extracted antigens are structurally and, in most cases, immunologically incomplete. They form the lower molecular weight core structures of their respective native antigens, which all contain additional terminal sialic acid residues (4)(5)(6)(7)(8). The structures of the types Ia, Ib, 11, and I11 capsular polysaccharides have been elucidated (9-1 l), and the important role of sialic acid in the pathogenicity of GBS (12) Can.…”

Protection from Group B Streptococcal Infection in Neonatal Mice by Maternal Immunization with Recombinant Sip Protein

“…They were shown to be safe, but their immunogenicity was disappointing (3,7). These CPS, when coupled to carrier proteins such as tetanus toxoid, were shown to be more immunogenic in preclinical animal assays (15,20,24,25,(30)(31)(32) and human clinical trials (5,6,13), and as expected, the protection was shown to be type specific (3,12,13). Based on the current information on serotype distribution, a conjugate vaccine would have to include types Ia, Ib, II, III, and V to prevent the majority of disease in North America.…”