MUCOSAL IMMUNOGENICITY OF POLYSACCHARIDES CONJUGATED TO A PEPTIDE OR MULTIPLE-ANTIGEN PEPTIDE-CONTAINING T-CELL AND B-CELL EPITOPES

In this study we investigated the mucosal and systemic responses to tw o T-cell-independent polysaccharides, a serogroup f polysaccharide (fo rmed of rhamnose glucose polymers [RGPs]) from Streptococcus mutans OM Z 175 and a mannan from Saccharomyces cerevisiae, covalently conjugate d either to a linear peptide (peptide 3) or to a multiple-antigen pept ide (MAP), both derived from S. mutans protein SR, an adhesin of the I /II protein antigen family of oral streptococci, Peptide:3 and MAP, wh ich contained at least one B- and one T-cell epitope, were tested as c arriers for the polysaccharides and as protective immunogens. Intragas tric intubation of rats with the conjugates (RGPs-peptide 3, RGPs-MAP, mannan-peptide 3, and mannan-MAP) associated with liposomes produced salivary immunoglobulin A (IgA) antibodies which reacted with RGPs or mannan, peptide 3 or MAP, protein SR, and S. mutans or S. cerevisiae c ells, Administration of conjugate boosters to the animals showed that both carriers conjugated to the polysaccharides were able to induce, i n immunized animals, a salivary antipolysaccharide IgA memory, In cont rast, animals primed and challenged with unconjugated polysaccharide s howed no anamnestic response, Rats orally immunized with the conjugate s also developed systemic primary antipolysaccharide and antipeptide I gM antibody responses which were characterized by a switch from IgM to IgG during the course of the secondary response, Data presented here demonstrated that both peptide 3 and the MAP construct can get as good carriers for orally administered polysaccharides. Unexpectedly, the u se of a MAP did not further improve the immunogenicity of polysacchari des at the mucosal level; nevertheless, such a construct should be of great interest in overcoming the problem of genetic restriction induce d by linear peptides.