Serum and salivary antibody responses in rats orally immunized with Streptococcus mutans carbohydrate protein conjugate associated with liposomes

Abstract

In this study we describe the preparation of a Streptococcus mutans vaccine consisting of a purified polysaccharide antigen, derived from S. mutans OMZ175 serotype f, covalently coupled through reductive amination to a previously isolated 74,000-molecular-weight (74K) cell wall protein which interacts with saliva proteins (74K-SR). We also investigated the local and systemic immune response to the poly-74K-SR conjugate after oral administration of the conjugate associated with liposomes. Intragastric administration of liposomeassociated poly-74K-SR conjugate in rats produced a local immunoglobulin A (IgA) response directed against the polysaccharide and the cell surface protein, whereas liposome-associated polysaccharide was unable to induce any detectable local IgA response. The antigenicity of the polysaccharide in the conjugate was not affected by the coupling reaction, while that of the cell surface protein was reduced. We showed that the immunogenicity of S. mutans polysaccharide could be improved by chemical coupling with a carrier cell surface protein. If such a conjugate were orally administered with liposomes it could constitute a potential vaccine against dental caries. 20:1061-1065. 24. Scholler, M., J. P. Klein, P. Sommer, and R. M. Frank. 1983. Common antigens of streptococcal and non streptococcal oral bacteria: characterization of wall-associated protein and com-INFECT. IMMUN. on August 5, 2020 by guest http://iai.asm.org/ Downloaded from

Distribution, persistence, and recall of serum and salivary antibody responses to peroral immunization with protein antigen I/II of Streptococcus mutans coupled to the cholera toxin B subunit

“…This is sometimes overcome by greatly increasing the dose of antigen to several milligrams per mouse (6,14,23). Other strategies for enhancing enteric immunogenicity include incorporation of the antigen into liposomes or microspheres, which protect the antigen against digestion and are more readily ingested by the M cells of Peyer's patches than soluble antigens (12,31,34,44). Because CTB has high affinity for GM, ganglioside, which is present on all nucleated cells, it is believed that this property is important for the immunogenicity of CT and CTB in the gut (18), and uptake of CT by intestinal epithelial cells has been reported (17).…”

Mucosal immunogenicity of polysaccharides conjugated to a peptide or multiple-antigen peptide containing T- and B-cell epitopes

“…Although this problem remains controversial (4) and needs further study, one way of circumventing the induction of this epitopic suppression could be to use a protein derived from the same microorganism to serve in the dual roles of carrier for the polysaccharide and protective immunogen. This was demonstrated by Wachsmann et al (29) in earlier studies in which conjugation of a serotype polysaccharide to a protein (SR), both of which originate from Streptococcus mutans OMZ 175 and are implicated in the bacterial virulence, induced an anamnestic response against the polysaccharide and the protein; these results have recently been confirmed by Madoff et al (16). Furthermore, as within protein SR, irrelevant determinants giving rise to autoantibodies (1) hindered the use of the whole protein; an SR-related immunogenic peptide, peptide 3 (13), containing B-and T-cell epitopes (14) was used instead of the SR protein and was successful in improving an anamnestic antipolysaccharide and antipeptide immune response (15).…”

“…For the determination of the B-cell epitope(s), the presence of anti-MAP antibodies in the sera of rats immunized with either rSR or MAP was assessed as described above, by using plates coated with MAP. Covalent linkage between RGPs or mannan and peptide 3 or MAP was checked by a heterologous two-site sandwich ELISA procedure as previously described by Wachsmann et al (29).…”

Mechanismen der Antigenaufnahme im Dünn- und Dickdarm: die Rolle der M-Zellen für die Initiierung von Immunantworten*

“…Für solche M-Zell-spezifischen Vakzine könnten zusätzlich Systeme zur gesteuerten Antigenfreisetzung benutzt werden, die einen Impfstoff über längere Zeit in die Umgebung abgeben und damit, im Vergleich zur einmaligen Gabe des reinen Antigens, zu einer ausgedehnten Stimulation führen [154,155]. Als Transportbehälter für solche verbesserten Oralimpfstoffe kämen Liposomen (künstliche Phospholipid-Membranvesikel; [156]), ISCOMs (lipophile immunstimulierende Komplexe; [157]) sowie resorbierbare Mikropartikel infrage [89,91]. Für die letzte Gruppe konnte gezeigt werden, dass diese Partikel relativ schnell über M-Zellen in die Peyer-Plaques transportiert werden [92,93].…”