Protective salivary immunoglobulin A responses against Streptococcus mutans infection after intranasal immunization with S. mutans antigen I/II coupled to the B subunit of cholera toxin

Abstract

The B subunit of cholera toxin (CTB) has been shown to augment mucosal responses to microbial virulence antigens, including those of Streptococcus mutans, which is the principal etiologic agent of dental caries. In the present study, the surface fibrillar protein antigen of S. mutans, antigen I/II (Ag I/I), was chemically coupled to CTB (Ag I/I-CTB), and the conjugate was examined for its effectiveness in inducing salivary immune responses protective against S. mutans infection. Weanling Fischer rats were given Ag I/II-CTB (50 p,g) by the intranasal route and then orally infected with a virulent strain of S. mutans. Gnotobiotic or conventional rats were given two or three additional immunizations, respectively, at about 2-week intervals. One week after each immunization, individual serum, saliva, and fecal samples were collected and stored frozen until assayed for antibody activity to Ag IJI and cholera toxin (CT) by an enzyme-linked immunosorbent assay. The rats were sacrificed 1 week after the last immunization, when mandibles were also collected from individual rats for assessment of S. mutans levels in plaque and caries activity. Rats immunized only or both immunized and infected showed a salivary immunoglobulin A (IgA) anti-Ag I/Il response which reached significantly (P < 0.05) higher levels than those seen in nonimmunized, infected controls. A salivary IgA anti-Ag I/II response was also seen in rats infected only with S. mutans. Essentially no salivary antibody activity to CT was detected. Some serum anti-Ag VII and anti-CT responses were seen in immunized animals. Serum IgG anti-Ag IJI responses were seen in immunized, infected rats and also in infected-only rats, suggesting that the responses were a result of infection with S. mutans. The immunized and infected rats had significantly (P < 0.05) lower levels of S. mutans in plaque and lower caries activity than nonimmunized, infected rats. These results indicated that intranasal immunization of rats with Ag I/I-CTB induced a protective salivary immune response which was associated with a reduction in S. mutans colonization and S. mutans-induced dental caries.

Properties of practical oral liposome‐Streptococcus mutans glucosyltransferase vaccines for effective induction of caries protection

“…Since all 4 groups of animals had anti-GTF antibody activity and the levels were not significantly different, it is possible that a response resulted from infection with S. mutans. Previous studies have reported early serum responses in rats after infection with S. mutans (14). Serum IgA anti-GTF activity in these animals increased later (day 47) and were higher in the experimental groups than in the control group, although the differences between groups were not significant.…”

Characterization of antigen‐presenting cells induced by intragastric immunization with recombinant chimeric immunogens constructed from Streptococcus mutans AgI/II and type I or type II heat‐labile enterotoxins

“…The Streptococcus mutans surface antigen AgI/II was originally identified as a potential antigen for developing a vaccine against caries (reviewed in Russell et al, 1999). We subsequently demonstrated that high levels of salivary IgA antibodies to AgI/II could be induced in rats or monkeys by mucosal immunization with AgI/II coupled to CTB, and that immunized rats were protected against caries (Katz et al, 1993;Russell et al, 1996). The N-terminal segment including the A-repeat region of AgI/II was found to be important in the adherence of S. mutans to saliva-coated hydroxyapatite (Hajishengallis et al, 1994), although others found that the central P-repeat region was also involved in adherence (Crowley et al, 1993).…”

Nasal Lymphoid Tissue (NALT) as a Mucosal Immune Inductive Site

“…Intranasal immunization can establish effective immunity against pneumococcal colonization in the upper respiratory tract, as well as protect mice from intratracheal challenge with virulent strains of pneumococci [5], block pharyngeal colonization by group A streptococci [6], protect mice from influenza virus infection [7], reduce Bordetella pertussis infection in mice [8], protect mice from i.n. herpes simplex virus challenge [9], and protect against Streptococcus mutans colonization on tooth surfaces [10,11]. However, the cells involved in generating this protection have not been defined.…”