Antígenos usados en vacunas contra la caries dental / Antigens Employed as Potential Vaccine against Dental Caries

Soledad Isabel Gómez Ramírez, Silvia Barrientos Sánchez

Abstract


La caries dental continúa siendo un problema de salud pública mundial, a pesar de medidas como la fluorización del agua y el incremento de los planes de prevención. Desde los años sesenta, cuando se consolidó el papel microbiano en la fisiopatología, se iniciaron estudios encaminados a desarrollar una vacuna con fines preventivos. El Streptococcus mutans (S. mutans), que es el principal microrganismo asociado, presenta tres antígenos importantes en la formación de la biopelícula: las glucosiltransferasas (GTF), la proteína de adhesión celular (PAc) y las proteínas fijadoras de glucanos (GBP). Estos antígenos proteicos participan en la colonización del microrganismo a la superficie del diente de diferentes formas: PAc es la responsable de la adhesión inicial a la superficie dental; las GTF, de la unión irreversible, y las GBP, de la unión a otras bacterias o coagregación. Cada una de estas proteínas ha sido estudiada en su conformación y mecanismo de acción, en búsqueda de la proteína óptima para inducir, en forma de vacuna, una respuesta inmune protectora frente a la caries. El objetivo del presente artículo es hacer un recuento de los aspectos más relevantes sobre estos antígenos y el estado actual del proceso de desarrollo de una vacuna con cada uno de ellos.

 

Dental caries remains a public health problem worldwide despite measures such as water fluoridation, and increased prevention plans. Since the 1960s when the paper of microbial pathophysiology was consolidated, studies began to develop a vaccine for prevention purposes. Streptococcus mutans (S. mutans), the main microorganism associated to dental decay have three relevant antigens in biofilm formation that are glucosyltransferases (GTFs), cell adhesion protein (PAc), and glucan binding proteins (GBP). These protein antigens involved in colonization of the microorganism to the surface of the tooth in different ways: PAc is responsible for the initial adhesion, irreversible binding GTF and GBP binding to other bacteria or coaggregation. Each of these proteins has been studied in their conformation and their mechanism of action aiming to induce optimal protein, as a vaccine, a protective immune response against caries. The aim of this review is to provide an account of the most relevant aspects of these antigens and the current status of the process of developing a vaccine to each of them.


Full Text:

PDF (Español)

References


Fontana M, Young DA, Wolff MS, Pitts NB, Longbottom C. Defining dental caries for 2010 and beyond. Dent Clin North Am. 2010 Jul; 54(3):423-40.

Fejerskov O. Changing paradigms in concepts on dental caries: consequences for oral health care. Caries Res. 2004 May-Jun; 38(3): 182-91.

Kidd EA, Fejerskov O. What constitutes dental caries? Histopathology of carious enamel and dentin related to the action of cariogenic biofilms. J Dent Res. 2004; 83(Spec issue): C35-C38.

Marsh PD. Dental plaque as a biofilm and a microbial community: Implications for health and disease. BMC Oral Health. 2006 Jun 15; 6(Suppl 1): S14.

Nicolas GG, Lavoie MC. Streptococcus mutans and oral streptococci in dental plaque. Can J Microbiol. 2011 Jan; 57(1): 1-20.

Takahashi N, Nyvad B. Caries ecology revisited: microbial dynamics and the caries process. Caries Res. 2008; 42(6): 409-18.

Socransky SS, Haffajee AD. Dental biofilms: difficult therapeutic targets. Periodontol 2000. 2002; 28: 12-55.

Bowen WH, Koo H. Biology of Streptococcus mutans-derived glucosyltransferases: role in extracellular matrix formation of cariogenic biofilms. Caries Res. 2011; 45(1): 69-86.

Loesche WJ. Microbiology of dental decay and periodontal disease. In: Baron S, editor. Medical microbiology. 4th ed. Galveston: University of Texas Medical Branch at Galveston; 1996.

Jaramillo LM, Gómez SI. Antígeno proteico de superficie celular (PAc) de Streptococcus mutans. Univ Odontol. 2004, 54-55: 125-31.

Taubman MA, Nash DA. The scientific and public health imperative for a vaccine against dental caries. Nat Rev Immunol. 2006 Jul; 6(7): 555-63.

Shivakumar KM, Vidya SK, Chandu GN. Dental caries vaccine. Indian J Dent Res. 2009 Jan-Mar; 20(1): 99-106.

Koga T, Oho T, Shimazaki Y, Nakano Y. Immunization against dental caries. Vaccine. 2002 May 15; 20(16): 2027-44.

Pecharki D, Petersen FC, Assev S, Scheie AA. Involvement of antigen I/II surface proteins in Streptococcus mutans and Streptococcus intermedius biofilm formation. Oral Microbiol Immunol. 2005 Dec; 20(6): 366-71.

Brady LJ, Maddocks SE, Larson MR, Forsgren N, Persson K, Deivanayagam CC, Jenkinson HF. The changing faces of Streptococcus antigen I/II polypeptide family adhesins. Mol Microbiol. 2010 Jul; 77(2): 276-86.

Russell MW, Lehner T. Characterization of antigens extracted from cells and culture fluids of Streptococcus mutans serotype c. Arch Oral Biol. 1978; 23(1): 7-15.

Matsumoto-Nakano M, Tsuji M, Inagaki S, Fujita K, Nagayama K, Nomura R, Ooshima T. Contribution of cell surface protein antigen c of Streptococcus mutans to platelet aggregation. Oral Microbiol Immunol. 2009 Oct; 24(5): 427-30.

Love RM, McMillan MD, Park Y, Jenkinson HF. Coinvasion of dentinal tubules by Porphyromonas gingivalis and Streptococcus gordonii depends upon binding specificity of streptococcal antigen I/II adhesin. Infect Immun. 2000 Mar; 68(3): 1359-65.

Zhang S, Green NM, Sitkiewicz I, Lefebvre RB, Musser JM. Identification and characterization of an antigen I/II family protein produced by group A Streptococcus. Infect Immun. 2006 Jul; 74(7): 4200-13.

Larson MR, Rajashankar KR, Crowley PJ, Kelly C, Mitchell TJ, Brady LJ, Deivanayagam C. Crystal structure of the C-terminal region of Streptococcus mutans antigen I/II and characterization of salivary agglutinin adherence domains. J Biol Chem. 2011 Jun 17; 286(24): 21657-66.

Jenkinson HF, Demuth DR. Structure, function and immunogenicity of streptococcal antigen I/II polypeptides. Mol Microbiol. 1997 Jan; 23(2): 183-90.

Chen F, Wang D. Novel technologies for the prevention and treatment of dental caries: a patent survey. Expert Opin Ther Pat. 2010 May; 20(5): 681-94.

Crowley PJ, Brady LJ, Piacentini DA, Bleiweis AS. Identification of a salivary agglutinin-binding domain within cell surface adhesin P1 of Streptococcus mutans. Infect Immun. 1993 Apr; 61(4): 1547-52.

Robinette RA, Oli MW, McArthur WP, Brady LJ. A therapeutic anti-Streptococcus mutans monoclonal antibody used in human passive protection trials influences the adaptive immune response. Vaccine. 2011 Aug 26; 29(37): 6292-300.

Li Y, Jin J, Yang Y, Bian Z, Chen Z, Fan M. Enhanced immunogenicity of an anti-caries vaccine encoding a cell-surface protein antigen of Streptococcus mutans by intranasal DNA prime-protein boost immunization. J Gene Med. 2009 Nov; 11(11): 1039-47.

Li LN, Guo LH, Lux R, Eckert R, Yarbrough D, He J, Anderson M, Shi WY. Targeted antimicrobial therapy against Streptococcus mutans establishes protective non-cariogenic oral biofilms and reduces subsequent infection. Int J Oral Sci. 2010 Jun; 2(2): 66-73.

Sullivan R, Santarpia P, Lavender S, Gittins E, Liu Z, Anderson MH, He J, Shi W, Eckert R. Clinical efficacy of a specifically targeted antimicrobial peptide mouth rinse: targeted elimination of Streptococcus mutans and prevention of demineralization. Caries Res. 2011; 45(5): 415-28.

Inaba E, Uematsu H, Nishiyama Y, Watanabe H, Senpuku H. The role of anti-PAc (361–386) peptide SIgA antibody in professional oral hygiene of the elderly. Gerodontol. 2009; 26: 259-67.

Zhao W, Zhao Z, Russell MW. 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. Mol Oral Microbiol. 2011 Jun; 26(3): 200-9.

Sun Y, Shi W, Yang JY, Zhou DH, Chen YQ, Zhang Y, Yang Y, He BX, Zhong MH, Li YM, Cao Y, Xiao Y, Li W, Yu J, Li YH, Fan MW, Yan HM. Flagellin-PAc fusion protein is a high-efficacy anti-caries mucosal vaccine. J Dent Res. 2012 Oct; 91(10): 941-7.

Xu Q, Katz J, Zhang P, Ashtekar AR, Gaddis DE, Fan M, Michalek SM. Contribution of a Streptococcus mutans antigen expressed by a Salmonella vector vaccine in dendritic cell activation. Infect Immun. 2011 Sep; 79(9): 3792-800.

Takehara T, Ansai T, Kunimori A, Yamashita Y, Hanada N. The extension of alpha-D- 1, 3 - branch linkages by 1,3-alpha-D-glucan synthase from Streptococcus sobrinus. FEMS Microbiol Lett. 1991 Sep 15; 67(1): 69-71.

Genco RJ, Emmings FG, Evans RT, Apicella M. Purification, characterization, and immunogenicity of cell-associated glucan from Streptococcus mutans. J Dent Res. 1976 Apr; 55(Spec issue): C115-C20.

Evans RT, Emmings FG, Genco RJ. Prevention of Streptococcus mutans infection of tooth surfaces by salivary antibody in Irus monkeys (Macacafascicularis). Infect Immun. 1975 Aug; 12(2): 293-302.

Chludzinski AM, Germaine GR, Schachtele CF. Purification and properties of dextransucrase from Streptococcus mutans. J. Bacteriol. 1974 Apr; 118(1): 1-7.

Koga T, Inoue M. Cellular adherence, glucosyltransferase adsorption, and glucan synthesis of Streptococcus mutans AHT mutants. Infect Immun. 1978 Feb; 19(2): 402-10.

Wenham DG, Davies RM, Cole JA. Insoluble glucan synthesis by mutans sucrase as a determinant of the cariogenicity of Streptococcus mutans. J Gen Microbiol. 1981 Dec; 127(2): 407-15.

Pucci MJ, Macrina FL. Cloned gtfA gene of Streptococcus mutans LM7 alters glucan synthesis in Streptococcus sanguis. Infect Immun. 1985 Jun; 48(3): 704-12.

Taubman MA, Smith DJ. A mucosal approach to immunoprophylaxis of dental infections. Adv Exp Med Biol. 1987; 216B: 1721-30.

Aires CP, Koo H, Sassaki GL, Iacomini M, Cury J A. A procedure for characterizing glucans synthesized by purified enzymes of cariogenic Streptococcus mutans. Int J Biol Macromol. 2010 Jun; 46(5): 551-4.

Hoshino T, Kondo Y , Saito K , Terao Y, Okahashi N, Kawabata Sh, Fujiwara T. Novel epitopic region of glucosyltransferase B from Streptococcus mutans. Clin Vaccine Immunol. 2011 Sep; 18(9): 1552-1561.

Chia JS, Yang CS, Chen JY. Functional analyses of a conserved region in glucosyltransferases of Streptococcus mutans. Infect Immun. 1998 Oct; 66(10): 4797-803.

Barrientos S, Rodríguez A Production of glucosyltransferase B and glucans by Streptococcus mutans strains isolated from caries-free individuals. Acta Odontol Latinoam. 2011; 24(3): 258-64.

Huang L, Xu QA, Liu C, Fan MW, Li YH. Anti-caries DNA vaccine-induced secretory immunoglobulin A antibodies inhibit formation of Streptococcus mutans biofilms in vitro. Acta Pharmacol Sin. 2012 Dec 31.

Taubman M, Holmberg C, Smith D. Diepitopic construct of functionally and epitopically complementary peptides enhances immunogenicity, reactivity with glucosyltransferase, and protection from dental caries. Infect Immun. 2001 July; 69(7): 4210-6.

Kirtaniya BC, Chawla HS, Tiwari A, Ganguly NK, Sachdev V. Natural prevalence of antibody titers to glucosyltransferase of Streptococcus mutans in serum in high and low caries active children. J Indian Soc Pedod Prev Dent. 2010 Apr-Jun; 28(2): 91-4.

Russell RR. Glucan-binding proteins of Streptococcus mutans serotype c. J Gen Microbiol. 1979 May; 112(1): 197-201.

Smith DJ, Akita H, King WF, Taubman MA. Purification and antigenicity of a novel glucan-binding protein of Streptococcus mutans. Infect Immun. 1994 Jun; 62(6): 2545-52.

Sato Y, Yamamoto Y, Kizaki H. Cloning and sequence analysis of the gbpC gene encoding a novel glucan-binding protein of Streptococcus mutans. Infect Immun. 1997 Feb; 65(2): 668-75.

Lynch DJ, Fountain TL, Mazurkiewicz JE, Banas JA. Glucan-binding proteins are essential for shaping Streptococcus mutans biofilm architecture. FEMS Microbiol Lett. 2007 Mar; 268(2): 158-65. Epub 2006 Dec 1.

Banas JA, Vickerman MM. Glucan-binding proteins of the oral streptococci. Crit Rev Oral Biol Med. 2003; 14(2): 89-99.

Nogueira RD, King WF, Gunda G, Culshaw S, Taubman MA, Mattos-Graner RO, Smith D. Mutans streptococcal infection induces salivary antibody to virulence proteins and associated functional domains. Infect Immun. 2008 Aug; 76(8): 3606-13. Epub 2008 May 12.


Article Metrics

Metrics Loading ...

Metrics powered by PLOS ALM




Copyright (c)

Creative Commons
This work is registered under Creative Commons Attribution 4.0 International.
Created from http://revistas.javeriana.edu.co/.