Immunogenic properties in mice of hexasaccharide from the capsular polysaccharide of Streptococcus pneumoniae type 3

Abstract

Hexasaccharide (HS) containing 3 U of cellobiuronic acid was isolated from Streptococcus pneumoniae type 3 capsular polysaccharide S3 and coupled to bovine serum albumin (BSA), keyhole limpet hemocyanin (KLH), or tetanus toxoid (TT). The immunogenicity of these HS-protein conjugates in BALB/c mice was studied by measuring the production of circulating antibodies and the induction of protective immunity to viable S. pneumoniae type 3. Immunization of BALB/c mice with 0.5 jig of S3 resulted in the induction of immunoglobulin M (IgM) antibodies and complete protection against 25 U of a mean lethal dose of S. pneumoniae type 3 for 19 weeks after immunization. BALB/c mice immunized with 100 ,ug of HSq-BSA (containing 12 ,ug of HS) were also protected due to circulating IgM antibodies. Repeated injections with either 100 ,ug of HSq-BSA (three immunizations) or 100 ,ug of HS6-KLH (two immunizations) resulted in high levels of circulating IgG antibodies. These HS-protein conjugates induced complete protection which lasted at least 14 (HS9-BSA), 23 (HS6-KLH), or 8 (HS16-TT) weeks after the last immunization. Protection against viable S. pneumoniae type 3 could be passively transferred to nonimmunized mice by antisera containing IgM or IgG antibodies or both. Sera containing both IgM and IgG antibodies gave better protection than sera containing only IgM antibodies. The specificity of the induced protection was confirmed by challenge with the non-cross-reacting S. pneumoniae type 11. Anti-capsular polysaccharide antibodies confer immunity to infections with Streptococcus pneumonia (10). These anti-polysaccharide antibodies exert their protective effect by opsonization. S. pneumoniae infections can be prevented by vaccination with purified capsular polysaccharides, and in 1977 a polyvalent pneumococcal polysaccharide was licensed for general use in the United States (1). Because vaccination aims at long-lasting protection against infectious

Carbohydrate based vaccines

“…The results fit well to previous studies [14,15], wherein it was shown that a hexasaccharide derived from polysaccharide type 3 coupled without spacer as a pentasaccharide to KLH was capable of inducing protective immunity against type 3 pneumococci in mice.…”

Immunogenic properties of octasaccharide-protein conjugates derived from Klebsiella serotype 11 capsular polysaccharide

“…In earlier experiments with Streptococcus pneumoniae type 3 capsular polysaccharide (S3PS) and hexasaccharideprotein conjugates, we showed that the S3PS behaved as a TI antigen, whereas the hexasaccharide-protein conjugates behaved as TD antigens (35). To extend the results obtained with S3PS and hexasaccharide-protein conjugates of S. pneumoniae, we used the capsular polysaccharide of Klebsiella serotype 11, K11PS, as a novel model antigen.…”

“…Since the OS-keyhole limpet hemocyanin conjugate induced antibodies in both (CBA/N x C3H/HeN)Fl females and males, we propose to refer to this kind of antigen as a thymus-dependent type 1 antigen, whereas OS-bovine serum albumin, which evoked immunoglobulins in (CBA/N x C3H/HeN)Fl females only, can be referred to as a thymus-dependent type 2 antigen.Bacterial polysaccharides are generally considered to be thymus-independent (TI) antigens (4, 6) and are characterized by the induction of mainly immunoglobulin M (IgM) and IgG3 antibodies after primary immunization (17, 29), without the induction of immunological memory (35). Moreover, the immune response toward TI antigens is developed only at later stages of the ontogeny, which has important consequences for the vaccination of neonates (27,35).For vaccinations aiming at long-lasting protection against diseases, it would be desirable to immunize with thymus-dependent (TD) antigens (35). TD antigens are supposed to induce immunological memory and thus to provoke a state of prolonged resistance to infections (36).…”

“…Bacterial polysaccharides are generally considered to be thymus-independent (TI) antigens (4,6) and are characterized by the induction of mainly immunoglobulin M (IgM) and IgG3 antibodies after primary immunization (17,29), without the induction of immunological memory (35). Moreover, the immune response toward TI antigens is developed only at later stages of the ontogeny, which has important consequences for the vaccination of neonates (27,35).…”

“…For vaccinations aiming at long-lasting protection against diseases, it would be desirable to immunize with thymus-dependent (TD) antigens (35). TD antigens are supposed to induce immunological memory and thus to provoke a state of prolonged resistance to infections (36).…”