Immunogenic and Protective Potential of Mutans Streptococcal Glucosyltransferase Peptide Constructs Selected by Major Histocompatibility Complex Class II Allele Binding

Culshaw, Shauna; LaRosa, Karen B.; Tolani, H.; Han, Xiaoping; Eastcott, J W; Smith, Daniel J.; Taubman, Martin A.

doi:10.1128/iai.01582-06

Cited by 18 publications

(12 citation statements)

References 32 publications

(37 reference statements)

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“…1) that had been associated either with putative regions containing functional activity or with peptides that had MHC class II binding activity. Several of these peptides (GGY, CAT, Pep 11, and GLU) previously had been shown to induce a protective immune response to infection with cariogenic mutans strep- tococci (7,31,41). Figure 4 shows the median postinfection increases in the FI/IgA antibody value for each of the peptides assayed with all 22 salivas from both experiments.…”

Section: Resultsmentioning

confidence: 99%

“…Two monoepitopic peptide construct sequences (GLB and GLU) were based on Gtf sequences associated with putative glucan binding domains in the C-terminal third of the Gtf protein (1,17,43). Of further interest, several of these peptides (SYI, GGY, CAT, GLU, and Pep 11) have been shown to induce protective immune responses to the cariogenic effects of S. mutans and/or S. sobrinus infection (7,31,38,41). The Gtf/GbpB locations and sequences of the peptides are shown in Fig.…”

Section: Animals For the Immunization Experimentmentioning

confidence: 99%

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Mutans Streptococcal Infection Induces Salivary Antibody to Virulence Proteins and Associated Functional Domains

Nogueira

King²,

Gunda

et al. 2008

Infect Immun

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The interplay between mucosal immune responses to natural exposure to mutans streptococci and the incorporation and accumulation of these cariogenic microorganisms in oral biofilms is unclear. An initial approach to explore this question would be to assess the native secretory immunity emerging as a consequence of Streptococcus mutans infection. To this end, we analyzed salivary immunoglobulin A (IgA) antibody to mutans streptococcal glucosyltransferase (Gtf) and glucan binding protein B (GbpB) and to domains associated with enzyme function and major histocompatibility complex (MHC) class II binding in two experiments. Salivas were collected from approximately 45-day-old Sprague-Dawley rats, which were then infected with S. mutans SJ32. Infection was verified and allowed to continue for 2 to 2.5 months. Salivas were again collected following the infection period. Pre-and postinfection salivas were then analyzed for IgA antibody activity using peptide-or protein-coated microsphere Luminex technology. S. mutans infection induced significant levels of salivary IgA antibody to Gtf (P < 0.002) and GbpB (P < 0.001) in both experiments, although the levels were usually far lower than the levels achieved when mucosal immunization is used. Significantly (P < 0.035 to P < 0.001) elevated levels of postinfection salivary IgA antibody to 6/10 Gtf peptides associated with either enzyme function or MHC binding were detected. The postinfection levels of antibody to two GbpB peptides in the N-terminal region of the six GbpB peptides assayed were also elevated (P < 0.031 and P < 0.001). Interestingly, the patterns of the rodent response to GbpB peptides were similar to the patterns seen in salivas from young children during their initial exposure to S. mutans. Thus, the presence of a detectable postinfection salivary IgA response to mutans streptococcal virulence-associated components, coupled with the correspondence between rat and human mucosal immune responsiveness to naturally presented Gtf and GbpB epitopes, suggests that the rat may be a useful model for defining mucosal responses that could be expected in humans. Under controlled infection conditions, such a model could prove to be helpful for unraveling relationships between the host response and oral biofilm development.

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Section: Resultsmentioning

confidence: 99%

Section: Animals For the Immunization Experimentmentioning

confidence: 99%

Mutans Streptococcal Infection Induces Salivary Antibody to Virulence Proteins and Associated Functional Domains

Nogueira

King²,

Gunda

et al. 2008

Infect Immun

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“…Delivery of antigens with appropriate adjuvants via mucosal routes increases anti-GTF salivary (secretory) IgA and serum IgG levels and protects against experimental caries. Anti-caries protection in animals was obtained after immunization with intact GTF or glucan binding protein (GBP), their derived synthetic peptides, recombinant peptide-enzyme fusion proteins or, even DNA vaccines encoding one or more target antigens or their fragments [149,150]. Clearly, proof of principle exists for a dental caries vaccine.…”

Section: Caries Microbiome and Immunitymentioning

confidence: 99%

The oral microbiome and the immunobiology of periodontal disease and caries

2014

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The composition of the oral microbiome differs from one intraoral site to another, reflecting in part the host response and immune capacity at each site. By focusing on two major oral infections, periodontal disease and caries, new principles of disease emerge. Periodontal disease affects the soft tissues and bone that support the teeth. Caries is a unique infection of the dental hard tissues. The initiation of both diseases is marked by an increase in the complexity of the microbiome. In periodontitis, pathobionts and keystone pathogens such as Porphyromonas gingivalis appear in greater proportion than in health. As a keystone pathogen, P. gingivalis impairs host immune responses and appears necessary but not sufficient to cause periodontitis. Historically, dental caries had been causally linked to Streptococcus mutans. Contemporary microbiome studies now indicate that singular pathogens are not obvious in either caries or periodontitis. Both diseases appear to result from a perturbation among relatively minor constituents in local microbial communities resulting in dysbiosis. Emergent consortia of the minor members of the respective microbiomes act synergistically to stress the ability of the host to respond and protect. In periodontal disease, host protection first occurs at the level of innate gingival epithelial immunity. Secretory IgA antibody and other salivary antimicrobial systems also act against periodontopathic and cariogenic consortia. When the gingival immune response is impaired, periodontal tissue pathology results when matrix metalloproteinases are released from neutrophils and T cells mediate alveolar bone loss. In caries, several species are acidogenic and aciduric and appear to work synergistically to promote demineralization of the enamel and dentin. Whereas technically possible, particularly for caries, vaccines are unlikely to be commercialized in the near future because of the low morbidity of caries and periodontitis.

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“…The adhesins interact with salivary proteins of the acquired pellicle on the tooth surface to promote adherence, glucosyltransferases catalyze glucan synthesis; Gbp increases the binding of MS to glucans deposited on tooth surfaces, contributing to the sucrose-dependent adherence to teeth [Lamont et al, 1991;Jenkinson et al, 1997]. Studies have shown that specific antibody induction to the above antigens [Taubman and Smith, 1977;Katz et al, 1993;Smith and Taubman, 1996], as well as to intrinsic peptides related to these antigens (such as QGQ, VAR, SYI, SIG, GGY, Pep 7, Pep 16, LVK, GLU), might prevent dental caries development in animal models [Smith et al, 1994a, b;Taubman et al, 1995;Smith et al, 1997Smith et al, , 1999Taubman et al, 2001;Smith et al, 2003Smith et al, , 2005Culshaw et al, 2007b]. Furthermore, some clinical trials [Smith and Taubman, 1990;Childers et al, 1999] suggest that adhesins I/II and Gtfs could be important in the development of vaccines [Smith, 2002;Smith and Mattos-Graner, 2008].…”

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confidence: 99%

Immunological and Microbiologic Changes during Caries Development in Young Children

Parisotto

King²,

Duque

et al. 2011

Caries Res

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We explored the association between caries development, colonization with caries-associated microflora, and immunity as children begin the transition to mixed dentition. Forty children received dental examinations at 3–4 years of age, repeated a year later. Children were grouped into caries-free (n = 23; CF) and caries-active (n = 17; CA ≧3 new lesions on follow-up). Salivary IgA and IgA antibody to Streptococcus mutans virulence epitopes were measured by Luminex assay. Mutans streptococci (MS), lactobacilli and total microorganisms were enumerated on selective media from plaque samples. There was no significant difference in baseline levels of MS or lactobacilli between CF and CA groups. However, both MS and lactobacilli levels were higher at follow-up in the CA group. Furthermore, children with detectable lactobacilli at baseline had significantly higher caries risk. Salivary IgA concentrations increased significantly in both groups during the study. Both CF and CA groups also displayed significant increases in salivary IgA antibody levels to glucosyltransferase, glucan-binding protein (Gbp) and antigen I/II salivary binding region. CF antibody levels to seven peptides associated with domains of biological importance increased at follow-up, in contrast to increases to only three peptides in CA saliva samples. Multivariate modeling showed that a lower baseline level of salivary IgA anti-GbpB was associated with higher caries risk. These data indicate that MS and lactobacilli are associated with caries in this population, that the secretory immune system is undergoing significant maturation during this period, and that the breadth of mucosal IgA response to epitopes of S. mutans virulence components may influence the degree to which these cariogenic microorganisms can cause disease.

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Immunogenic and Protective Potential of Mutans Streptococcal Glucosyltransferase Peptide Constructs Selected by Major Histocompatibility Complex Class II Allele Binding

Cited by 18 publications

References 32 publications

Mutans Streptococcal Infection Induces Salivary Antibody to Virulence Proteins and Associated Functional Domains

Mutans Streptococcal Infection Induces Salivary Antibody to Virulence Proteins and Associated Functional Domains

The oral microbiome and the immunobiology of periodontal disease and caries

Immunological and Microbiologic Changes during Caries Development in Young Children

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