A new approach in the development of a dental caries vaccine
https://doi.org/10.29235/1814-6023-2024-21-2-104-115
Abstract
The genomes of the bacteria Streptococcus mutans and Streptococcus sobrinus, which cause dental caries, currently have been fully sequenced. However, the secondary and tertiary structures of the full-size surface proteins of these microorganisms, by which they attach to the surface of teeth covered with saliva, have not been instrumentally determined at the moment. There are a number of experimental studies on the use of these proteins in the process of developing a dental caries vaccine. However, there is currently no commercially available dental caries vaccine.
The aim of the study was to choose an antigen for subsequent molecular modeling of a unique peptide for the development of a dental caries vaccine.
To develop an effective and safe dental caries vaccine, it is necessary to perform a number of experiments in silico, preceding experiments in vitro and in vivo. Today, this approach is not only generally recognized, but also allows to significantly reduce the cost of experiments and time at the preclinical and clinical studies. According to our hypothesis, as an antigen for the development of a dental caries vaccine, it is necessary to use a short fragment of the surface protein (a peptide) of Streptococcus mutans and/or Streptococcus sobrinus, whose homology in amino acid sequence is 84.8 %, the spatial structure of which should correspond to the spatial structure of the corresponding fragment in a full-sized protein. In addition, the selected protein fragment, which will be part of the vaccine peptide, must be available to antibodies, i. e. located on the surface of the protein and defined as a B-cell linear and spatial epitope. Also, according to our hypothesis, the vaccine peptide may consist of the most stable fragments of alanine and proline rich regions of the surface protein of Streptococcus mutans and/or Streptococcus sobrinus for mutual stabilization of the spatial structure.
About the Authors
S. P. RubnikovichBelarus
Sergeу P. Rubnikovich – Corresponding Member, D. Sc. (Med.), Professor, Rector
83, Dzerzhinski Ave., 220116, Minsk
V. V. Poboinev
Belarus
Victor V. Poboinev – Senior Lecturer
83, Dzerzhinski Ave., 220116, Minsk
V. V. Khrustalev
Belarus
Vladislav V. Khrustalev – D. Sc. (Biol.), Associate Professor, Head of the Department
83, Dzerzhinski Ave., 220116, Minsk
References
1. Rubnikovich S. P. (ed.). Dentistry: collection of clinical protocols. Pt. 1. Minsk, Belarusian State Medical University, 2023. 468 p. (in Russian).
2. Yu Y. B., Liu Y., Liang H., Dong X., Yang X. Y., Li S., Guo Z. A nanoparticle-based anticaries vaccine enhances the persistent immune response to inhibit streptococcus mutans and prevent caries. Microbiology Spectrum, 2023, vol. 11, no. 2, p. e0432822. https://doi.org/10.1128/spectrum.04328-22
3. Zhang Y., Wang X., Li H., Ni C., Du Z., Yan F. Human oral microbiota and its modulation for oral health. Biomedicine & Pharmacotherapy, 2018, vol. 99, pp. 883–893. https://doi.org/10.1016/j.biopha.2018.01.146
4. Smith D. J. Dental caries vaccines: prospects and concerns. Critical Reviews in Oral Biology and Medicine, 2002, vol. 13, no. 4, pp. 335–349. https://doi.org/10.1177/154411130201300404
5. Patel M. Dental caries vaccine: are we there yet? Letters in Applied Microbiology, 2020, vol. 70, no. 1, pp. 2–12. https://doi.org/10.1111/lam.13218
6. Forssten S. D., Björklund M., Ouwehand A. C. Streptococcus mutans, caries and simulation models. Nutrients, 2010, vol. 2, no. 3, pp. 290–298. https://doi.org/10.3390/nu2030290
7. Zhang J. S., Chu C. H., Yu O. Y. Oral microbiome and dental caries development. Dentistry Journal (Basel), 2022, vol. 10, no. 10, art. 184. https://doi.org/10.3390/dj10100184
8. Talbman M. A., Smith D. J. Effects of local immunization with Streptococcus mutans on induction of salivary immunoglobulin A antibody and experimental dental caries in rats. Infection and Immunity, 1974, vol. 9, no. 6, pp. 1079–1091. https://doi.org/10.1128/iai.9.6.1079-1091.1974
9. McGhee J. R., Michalek S. M., Webb J., Navia J. M., Rahman A. F., Legler D. W. Effective immunity to dental caries: protection of gnotobiotic rats by local immunization with Streptococcus mutans. Journal of Immunology, 1975, vol. 114, no. 1, pt. 2, pp. 300–305. https://doi.org/10.4049/jimmunol.114.1_part_2.300
10. Russell R. R. Wall-associated protein antigens of Streptococcus mutans. Journal of General Microbiology, 1979, vol. 114, no. 1, pp. 109–115. https://doi.org/10.1099/00221287-114-1-109
11. Ackermans F., Klein J. P., Ogier J., Bazin H., Cormont F., Frank R. M. Purification and characterization of a salivainteracting cell wall protein from Streptococcus mutans serotype f by using monoclonal antibody immunoaffinity chromatography. Biochemical Journal, 1985, vol. 228, no. 1, pp. 211–217. https://doi.org/10.1042/bj2280211
12. Hughes M, Machardy S. M., Sheppard A. J., Woods N. C. Evidence for an immunological relationship between Streptococcus mutans and human cardiac tissue. Infection and Immunity, 1980, vol. 27, no. 2, pp. 576–588. https://doi.org/10.1128/iai.27.2.576-588.1980
13. Demuth D. R., Lammey M. S., Huck M., Lally E. T., Malamud D. Comparison of Streptococcus mutans and Streptococcus sanguis receptors for human salivary agglutinin. Microbial Pathogenesis, 1990, vol. 9, no. 3, pp. 199–211. https://doi.org/10.1016/0882-4010(90)90022-i
14. Crowley P. J., Brady L. J., Michalek S. M., Bleweis A. S. Virulence of a spaP mutant of Streptococcus mutans in a gnotobiotic rat model. Infection and Immunity, 1999, vol. 67, no. 3, pp. 1201–1206. https://doi.org/10.1128/iai.67.3.1201- 1206.1999
15. Lehner T., Russell M. W., Caldwell J., Smith R. Immunization with purified protein antigens from Streptococcus mutans against dental caries in rhesus monkeys. Infection and Immunity, 1981, vol. 34, no. 2, pp. 407–415. https://doi.org/10.1128/iai.34.2.407-415.1981
16. Redman T. K., Harmon C. C., Michalek S. M. Oral immunization with recombinant Salmonella typhimurium expressing surface protein antigen A (SpaA) of Streptococcus sobrinus: effects of the Salmonella virulence plasmid on the induction of protective and sustained humoral responses in rats. Vaccine, 1996, vol. 14, no. 9, pp. 868–878. https://doi.org/10.1016/0264-410x(96)00013-8
17. Takahashi I., Okahashi N., Matsushita K., Tokuda M., Kanamoto T., Munekata E., Russell M. W., Koga T. Immunogenicity and protective effect against oral colonization by Streptococcus mutans of synthetic peptides of a streptococcal surface protein antigen. Journal of Immunology, 1991, vol. 146, no. 1, pp. 332–336. https://doi.org/10.4049/jimmunol.146.1.332
18. Brady L. J., Maddocks S. E., Larson M. R. Forsgren N., Persson K., Deivanayagam C. C., Jenkinson H. F. The changing faces of Streptococcus antigen I/II polypeptide family adhesins. Molecular Microbiology, 2010, vol. 77, no. 2, pp. 276–286. https://doi.org/10.1111/j.1365-2958.2010.07212.x
19. Nakai M., Okahashi N., Ohta H., Koga T. Saliva-binding region of Streptococcus mutans surface protein antigen. Infection and Immunity, 1993, vol. 61, no. 10, pp. 4344–4349. https://doi.org/10.1128/iai.61.10.4344-4349.1993
20. LaPolla R. J., Haron J. A., Kelly C. G., Taylor W. R., Bohart C., Hendricks M., Pyati J. P., Graff R. T., Ma J. K., Lehner T. Sequence and structural analysis of surface protein antigen I/II (SpaA) of Streptococcus sobrinus. Infection and Immunity, 1991, vol. 59, no. 8, pp. 2677–2685. https://doi.org/10.1128/iai.59.8.2677-2685.1991
21. Giasuddin A. S. M., Huda S., Jhuma K. A., Haq A. M. Dental caries vaccine availability: Challenges for the 21st century. Journal of Immunology and Immunotherapy, 2017, vol. 1, no. 7, art. 100002.
22. Ayakawa G. Y., Siegel J. L., Crowley P. J., Bleiweis A. S. Immunochemistry of the Streptococcus mutans BHT cell membrane: detection of determinants cross-reactive with human heart tissue. Infection and Immunity, 1985, vol. 48, no. 2, pp. 280–286. https://doi.org/10.1128/iai.48.2.280-286.1985
23. Nakano K., Tsuji M., Nishimura K., Nomura R., Ooshima T. Contribution of cell surface protein antigen PAc of Streptococcus mutans to bacteremia. Microbes and Infection, 2006, vol. 8, no. 1, pp. 114–121. https://doi.org/10.1016/j.micinf.2005.06.005
24. Batista M. T., Ferreira E. L., Pereira G. S., Stafford P., Maeda D. L. N. F., Rodrigues J. F., Brady L. J., Johnston S. A., Ferreira L. C. S., Ferreira R. C. C. LT adjuvant modulates epitope specificity and improves the efficacy of murine antibodies elicited by sublingual vaccination with the N-terminal domain of Streptococcus mutans P1. Vaccine, 2017, vol. 35, no. 52, pp. 7273–7282. https://doi.org/10.1016/j.vaccine.2017.11.007
25. Apweiler R., Bairoch A., Wu C. H., Barker W. C., Boeckmann B., Ferro S. [et al.]. UniProt: the universal protein knowledgebase. Nucleic Acids Research, 2004, vol. 32, pp. D115–D119. https://doi.org/10.1093/nar/gkh131
26. Jumper J., Evans R., Pritzel A., Green T., Figurnov M., Ronneberger O. [et al.]. Highly accurate protein structure prediction with AlphaFold. Nature, 2021, vol. 596, no. 7873, pp. 583–589. https://doi.org/10.1038/s41586-021-03819-2
27. Poboinev V. V., Khrustalev V. V., Khrustaleva T. A., Kasko T. E., Popkov V. D. The PentUnFOLD algorithm as a tool to distinguish the dark and the light sides of the structural instability of proteins. Amino Acids, 2022, vol. 54, no. 8, pp. 1155–1171. https://doi.org/10.1007/s00726-022-03153-5
28. Khrustalev V. V. The PentaFOLD 3.0 algorithm for the selection of stable elements of secondary structure to be included in vaccine peptides. Protein and Peptide Letters, 2021, vol. 28, no. 5, pp. 573–588. https://doi.org/10.2174/0929866527666201110123851
29. Smith T. F., Waterman M. S. Identification of common molecular subsequences. Journal of Molecular Biology, 1981, vol. 147, no. 1, pp. 195–197. https://doi.org/10.1016/0022-2836(81)90087-5
30. Eisenberg D., Lüthy R., Bowie J. U. VERIFY3D: assessment of protein models with three-dimensional profiles. Methods in Enzymology, 1997, vol. 277, pp. 396–404. https://doi.org/10.1016/s0076-6879(97)77022-8
31. Laskowski R. A., MacArthur M. W., Moss D. S., Thornton J. M. PROCHECK: a program to check the stereochemical quality of protein structures. Journal of Applied Crystallography, 1993, vol. 26, pp. 283–291. https://doi.org/10.1107/s0021889892009944
32. Heim K. P., Crowley P. J., Long J. R., Kailasan S., McKenna R., Brady L. J. An intramolecular lock facilitates folding and stabilizes the tertiary structure of Streptococcus mutans adhesin P1. Proceedings of the National Academy of Sciences of the United States of America, 2014, vol. 111, no. 44, pp. 15746–15751. https://doi.org/10.1073/pnas.1413018111
33. Baker E. G., Williams C., Hudson K. L., Bartlett G. J., Heal J. W., Porter Goff K. L., Sessions R. B., Crump M. P., Woolfson D. N. Engineering protein stability with atomic precision in a monomeric miniprotein. Nature Chemical Biology, 2017, vol. 13, no. 7, pp. 764–770. https://doi.org/10.1038/nchembio.2380
34. Khrustalev V. V., Kordyukova L. V., Arutyunyan A. M., Poboinev V. V., Khrustaleva T. A., Stojarov A. N., Baratova L. A., Sapon A. S., Lugin V. G. The cytoplasmic tail of influenza A/H1N1 virus hemagglutinin is β-structural. Journal of Biomolecular Structure and Dynamics, 2022, vol. 40, no. 10, pp. 4642–4661. https://doi.org/10.1080/07391102.2020.1860827
35. Poboinev V. V., Khrustalev V. V., Akunevich A. A., Shalygo N. V., Stojarov A. N., Khrustaleva T. A., Kordyukova L. V. Peptide models of the cytoplasmic tail of influenza A/H1N1 virus hemagglutinin expand understanding its pH-dependent modes of interaction with matrix protein M1. Protein Journal, 2023, vol. 42, no. 4, pp. 288–304. https://doi.org/10.1007/s10930-023-10101-z
Review
For citations:
Rubnikovich S.P., Poboinev V.V., Khrustalev V.V. A new approach in the development of a dental caries vaccine. Proceedings of the National Academy of Sciences of Belarus, Medical series. 2024;21(2):104-115. (In Russ.) https://doi.org/10.29235/1814-6023-2024-21-2-104-115