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

Abstract

In the present study, we compared the ability of the soluble adjuvants concanavalin A (ConA), muramyl dipeptide (MDP), and peptidoglycan (PG) to enhance immune responses to orally administered particulate antigens of Streptococcus mutans 6715 in gnotobiotic rats. The isotype and levels of antibody in saliva and in serum from experimental rats were determined by an enzyme-linked immunosorbent assay using S. mutans whole cells (WC) as the coating antigen. The specificities of salivary and serum immunoglobulin A (IgA) antibodies to particulate S. mutans antigens, lipoteichoic acid, S. mutans serotype g carbohydrate, and dextran were also determined. When 50 ,ug of ConA was used as the oral adjuvant with S. mutans 6715 WC immunogen, a slight enhancement of immune responses was obtained. A higher dose of ConA suppressed humoral responses to the immunogen. Enhanced immune responses, especially of the IgA isotype, in both serum and saliva were induced in gnotobiotic rats given MDP and either S. mutans 6715 WC or purified cell walls (CW) by gastric intubation. Elevated IgA antibody levels to CW, lipoteichoic acid, and carbohydrate were observed in rats given S. mutans WC and MDP by gastric intubation, whereas oral immunization with S. mutans CW and MDP resulted in higher antibody levels to CW and carbohydrate and lower levels to lipoteichoic acid when compared with the antibody levels in rats given antigen alone. Rats orally immunized with either S. mutans WC or CW and MDP and challenged with virulent S. mutans 6715 exhibited significantly (P < 0.05) lower plaque scores, numbers of viable S. mutans in plaque, and caries scores than did rats immunized with antigen alone or in infected-only controls. In another series of experiments, a PG fraction derived from S. mutans 6715 CW was assessed for adjuvant properties. The oral administration of PG and either S. mutans WC or CW induced good salivary and serum IgA antibody responses. The specificity of the antibodies was similar to that obtained in rats given antigen and MDP. Rats receiving either S. mutans WC or CW and PG and challenged with virulent S. mutans 6715 had lower plaque scores, fewer numbers of viable S. mutans in plaque, and lower caries activity than did infected rats receiving S. mutans WC or CW immunogen alone. These results provide evidence that soluble adjuvants derived from the gram-positive bacterial CW, e.g., MDP and PG, are effective oral adjuvants and augment

Promotion of Ulcerative Duodenitis in Young Ferrets by Oral Immunization with Helicobacter mustelae and Muramyl Dipeptide

“…Selection of MDP as an alternative adjuvant was supported by evidence that it is the active structure of bacterial peptidoglycans with adjuvant properties and activates macrophage adherence, spreading, chemotaxis, phagocytosis, and release of interleukin 1 [35]. MDP has been shown to enhance the in vitro and in vivo immune responses of mice and rats when given orally to boost the immune response against both nonreplicating and replicating antigens [21,22,36,37].…”

Oral immunization of humans with dehydrated liposomes containing Streptococcus mutans glucosyltransferase induces salivary immunoglobulin A2 antibody responses

“…Percentage increase in individual salivary IgA, (top) and IgA, (bottom) anti-GTF response after oral immunization with rehydrated liposome-GTF. Values are the percentage increase (above 50%) over baseline in patotid saliva satnples collected frotn 7 subjects after oral itnmunization wilh liposotne-GTF (taken daily on days 0-2 and then [28][29][30]. Values represent the percentage inctease in the ratio of anli-GTF antibody aclivily/tolal IgA subclass over 2 pte-imtnunization values.…”

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.…”

“…Thus, oral administration of S. mutans antigens to rats has resulted in the production of salivary immunoglobulin A (IgA) antibodies, which can protect against dental caries (27). This local synthesis of specific antibodies can be enhanced by the use of adjuvant such as muramyl dipeptide or liposomes (18,26,28).…”