Enhancement of Murine Immune Responses to Orally Administered Haptenated Streptococcus mutans

Abstract

The induction of immune responses to orally administered trinitrophenyl (TNP)-haptenated Streptococcus mutans and its enhancement with muramyldipeptide (MDP), peptidoglycan (PG), and concanavalin A (Con A) were investigated in lipopolysaccharide (LPS)-non-responsive C3H/HeJ mice and the syngeneic, LPS-responsive C3H/HeN strain. Both mouse strains manifested similar immune responses, primarily of the IgM isotype, after a single gastric intubation (GI) with TNP-S. mutans. However, when groups of animals were first carrier-primed by GI with S. mutans for 2 consecutive days, followed by a single GI with TNP-S. mutans 1 week later, C3H/HeJ mice gave a significantly higher (P less than or equal to 0.01) splenic IgA anti-TNP plaque-forming cell (PFC) response than identically treated C3H/HeN mice. Furthermore, saliva, urine and serum from these C3H/HeJ mice possessed high levels of IgA anti-TNP antibodies as determined by the enzyme-linked immunosorbent assay, whereas C3H/HeN mice exhibited low antibody levels. Oral administration of Con A (either 250 micrograms or 500 micrograms/mouse) or purified PG (1 mg/mouse) at the time of TNP-S. mutans immunization resulted in significantly (P less than or equal to 0.01) enhanced splenic IgA anti-TNP PFC responses, especially in C3H/HeJ mice. On the other hand, MDP promoted IgA anti-TNP PFC responses in LPS-responsive C3H/HeN mice but did not augment responses in C3H/HeJ animals. A similar immune response pattern was seen when antibody levels were measured in serum, saliva, and urine of both mouse strains. These results demonstrate that haptenated S. mutans is a good antigen for the induction of high IgA responses in orally immunized C3H/HeJ mice and that this high response can be enhanced with the adjuvants Con A and PG. However, MDP is ineffective in C3H/HeJ mice but enhances IgA responses in normal LPS-responsive C3H/HeN animals.

Effective immunity to dental caries: enhancement of salivary anti-Streptococcus mutans antibody responses with oral adjuvants

“…In the study reported here, we have shown that the oral administration of particulate S. mutans antigens with either MDP or S. mutans CW-derived PG results in enhanced salivary IgA anti-S. mutans antibody levels. This finding was not totally unexpected since we have previously shown that the oral administration of trinitrophenyl (TNP)-haptenated S. mutans and either MDP or PG to mice results in enhanced anti-TNP plaque-forming-cell and antibody responses (14). Furthermore, it is well known that MDP exhibits adjuvant properties for a number of antigens when administered by the oral route (3).…”

“…Since PG is a major component of the S. mutans CW, we considered the possibility that adjuvant derivatives from this structure could be used in an oral vaccine against dental caries. Our previous studies (14) have indicated that the oral administration of PG with haptenated S. mutans to mice enhanced splenic plaque-forming-cell responses, especially of the IgA isotype. Therefore, in the next series of experiments, gnotobiotic rats were given S. mutans 6715 WC or purified CW either alone or together with purified S. mutans PG by GI.…”

“…In this regard, previous studies have shown that the soluble molecular adjuvants concanavalin A (ConA), lipopolysaccharide (LPS), and muramyl dipeptide (MDP) enhance in vitro immune responses to thymic-dependent antigens in murine Peyer patch (PP) cell cultures (12,13). Furthermore, the oral administration of ConA with either bacterial (14) or erythrocyte (11) antigen results in enhanced murine IgA responses. Studies by Taubman and co-workers (38) indicate that GI of GTF and MDP to rats results in elevated salivary IgA antibody responses when compared with animals given GTF only.…”

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

“…Effective immunity against dental caries in rats, obtained after oral administration of S. mutans (14), is generally associated with the presence in saliva of antibodies directed against several cell wall components, including lipoteichoic acids, serotype polysaccharide, and cell wall proteins (12,18). However, immunity and protection are not restricted to vaccination with whole bacteria, and proteins or polysaccharides could act as active antigens in animals.…”

Mucosal T Cell Networks: Role of FcαR+T Cells and Ig BFαin Regulation of the IgA Response

“…Oral administration of T cell dependent (TD) antigens such as SRBC or whole bacteria results in Th cell induction in PP [45,471 and in subsequent IgA responses in spleen and in external secretions [45,47,62]. Furthermore, purified Th cells from PP of mice given antigen by the oral route, when added to normal splenic B cell cultures and immunized with the homologous oral-priming antigen, support IgM, IgG and mainly IgA responses [47] ( Table I).…”