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The Effect of Experimental BCG Antigen–Betulin-Derived Conjugates on the Guinea Pig Immunological Response

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Abstract

The immunopotentiating properties of BCG vaccine strain antigen conjugated with betulin derivatives have been evaluated. The experiments were carried out on agouti guinea pigs (n = 20). The animals of the experimental groups (n = 5) were immunized with the following antituberculosis drugs: group 1, with antigens of the BCG vaccine strain conjugated with betulinic acid; group 2, with BCG antigens conjugated with betulonic acid; and group 3, with the BCG vaccine. The animals of the control group (n = 5) were injected with a saline solution. All the animals were infected with a virulent culture of Mycobacterium bovis (strain 8) on day 30 after the administration of antituberculosis drugs. The blood sampling for the assessment of the immune status was conducted on day 30 after the administration of drugs and day 30 after the infection with M. bovis. The designed conjugates were found to display immunopotentiating activity characterized by a 1.7–3.8-fold increase in the number of immunocompetent cells and an increase in the neutrophil functional activity observed to a greater degree in the guinea pig group 2. After infection with M. bovis some key parameters of the immune system, such as a T-lymphocyte count and the activity of enzymatic (myeloperoxidase) and nonenzymatic (cationic proteins) bactericidal systems of neutrophilic granulocytes significantly increased in groups 2 and 3, which implied the highest antituberculosis activity of the agents administered to these animals. The guinea pigs were euthanized 45 days after the infection with M. bovis. The next pathoanatomical experiments proved that the vaccine strain conjugates with betulonic acid and the BCG vaccine induced marked resistance against the pathogenic mycobacteria. The protection indexes for these agents were approximately the same and achieved 66 and 71%, respectively.

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REFERENCES

  1. Tolstikov G.A., Flekhter, O.B., Shul’ts, E.E., Baltina, L.A., and Tolstikov, A.G., Khim. Interesakh Ustoich. Razvit., 2005, no. 13, pp. 1–30.

  2. Pisha, E., Chai, H., Lee, I.S., Chagweder, I.E., Farnsworth, N.R., Cordell, G.A., Beecher, C.W.W., Fong, H.H.S., Kinghorn, A.D., Brown, D.M., Wani, M.C., Wall, M.E., Hieken, T.J., Das Gupta, T.K., and Pezzuto, J.M., Nat. Med., 1995, vol. 1, pp. 1046–1051.

    Article  CAS  Google Scholar 

  3. Kazakova, O.B., Smirnova, I.E., Baltina, L.A., Boreko, E.I., Savinova, O.V., and Pokrovskii, A.G., Russ. J. Bioorg. Chem., 2018, vol. 44, pp. 740–744. https://doi.org/10.1134/S1068162018050059

    Article  CAS  Google Scholar 

  4. Kazakova, O.B., Smirnova, I.E., Medvedeva, N.I., Lopatina, T.V., Chudov, I.V., Sharipov, A.R., Ziganshin, A.S., and Tran Thi Phuong Thao, Russ. J. Bioorg. Chem., 2019, vol. 45, pp. 558–565. https://doi.org/10.1134/S1068162019050030

    Article  CAS  Google Scholar 

  5. Selzer, E., Thallinger, C., Hoeller, C., Oberkleiner, P., Wacheck, V., Pehamberger, H., and Jansen, B., Mol. Med., 2002, vol. 8, pp. 877–884.

    Article  CAS  Google Scholar 

  6. Recio, C.M., Giner, R.M., Manez, S., Gueho, J., Julien, H.R., Hostettmann, K., and Rios, J.L., Planta Med., 1995, vol. 61, pp. 9–12.

    Article  CAS  Google Scholar 

  7. Fujioka, T., Kashiwada, Y., Kilkuskie, R., Cosentino, L.M., Ballas, L.M., Jiang, J.B., Janzen, W.P., Chen, I.S., and Lee, K.H., J. Nat. Prod., 1994, vol. 57, pp. 243–247.

    Article  CAS  Google Scholar 

  8. Kashiwada, Y., Hashimoto, F., Cosentino, L.M., Chen, C.H., Garrett, P.E., and Lee, K.H., J. Med. Chem., 1996, vol. 39, pp. 1016–1017.

    Article  CAS  Google Scholar 

  9. Goldyrev, A.A., Deev, L.E., and Sitnikov, V.A., Agrar. Nauka, 2007, no. 11, pp. 26–28.

  10. Shcheglovitova, O.N., Shulyak, A.F., and Velichko, G.N., Ross. Vet. Zh. S.-Kh. Zhivotn., 2007, no. 1, pp. 31–33.

  11. Zadorozhnaya, M.V., Ptitsevodstvo, 2011, no. 4, pp. 61–62.

  12. Zadorozhnaya, M.V., Lysko, S.B., and Krasikov, A.P., Ptitsa Ptitseprod., 2012, no. 4, pp. 43–45.

  13. Caminiti, A., Pelone, F., Battisti, S., Gamberale, F., Colafrancesco, R., Sala, M., La Torre, M., Della Marta, U., and Scaramozzino, P., Transbound. Emerg. Dis., 2017, vol. 64, pp. 1493–1504. https://doi.org/10.1111/tbed.12540

    Article  CAS  PubMed  Google Scholar 

  14. Ciaravino, G., Ibarra, P., Casal, E., Pastor, LopezS., Espluga, J., Casal, J., Napp, S., and Allepuz, A., Front. Vet. Sci., 2017, vol. 4, article 202. https://doi.org/10.3389/fvets.2017.00202

    Article  PubMed  PubMed Central  Google Scholar 

  15. Allen, A.R., Skuce, R.A., and Byrne, A.W., Front. Vet. Sci., 2018, vol. 5, article 109. https://doi.org/10.3389/fvets.2018.00109

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  16. Mingaleev, D.N., Hisamutdinov, A.G., Efimova, M.A., Trubkin, A.I., and Kamalieva, J.R., BIO Web Conf., 2020, vol. 17, article 00115. https://doi.org/10.1051/bioconf/20201700115

  17. Parlane, N.A. and Buddle, B.M., Curr. Clin. Microbiol. Rep., 2015, vol. 2, pp. 44–53. https://doi.org/10.1007/s40588-014-0009-4

    Article  Google Scholar 

  18. Balseiro, A., Jobin, T., Gortázar, C., and Risalde, M.A., Pathogens, 2020, vol. 9, p. 472. https://doi.org/10.3390/pathogens9060472

    Article  CAS  PubMed Central  Google Scholar 

  19. Li, J., Zhao, A., Tang, J., Wang, G., Shi, Y., Zhan, L., and Qin, C., Eur. J. Clin. Microbiol. Infect. Dis., 2020, vol. 39, pp. 1405–1425. https://doi.org/10.1007/s10096-020-03843-6

    Article  PubMed  Google Scholar 

  20. Gurvich, A.E., Immunosorbenty i ikh ispol’zovanie v biotekhnologii (Immunosorbents and Their Use in Biotechnology), Moscow: Akad. Med. Nauk SSSR, Nauchno-Issled. Inst. Epidemiol. Mikrobiol. im. N.F. Gamalei, 1986, pp. 3–22.

  21. Bazhin, M.A. and Shamov, V.V., Aktual’nye problemy brutselleza i tuberkuleza zhivotnykh: sb. nauch. tr. VNIIBTZh (Actual Problems of Brucellosis and Tuberculosis of Animals: Collection of Scientific Papers of All-Russia Research Institute of Brucellosis and Tuberculosis of Animals). Omsk: Poligraf. Tsentr Ch.P. Kukhar G.G., 2000, pp. 61–66.

  22. Vlasenko, V.S., Shuliko, E.M., Petrov, S.Yu., Bazhin, M.A., and Novikov, A.N., Dostizh. Nauki Tekhn. Agroprom. Kompl. 2009, no. 12, pp. 47–49.

  23. Krasil’nikov, I.V., Nikolaeva, A.M., and Mashin, V.V., Sib. Med. Zh. (Tomsk), 2011, vol. 26, no. 2-2, pp. 65–67.

  24. Krasil'nikov I.V., Arakelov, S.A., and Petrovskii, S.V., Med. Alfavit, 2017, vol. 1, no. 8 (305), pp. 24–29.

  25. Flekhter, O.B., Karachurina, L.T., Nigmatullina, L.P., Baltina, L.A., Zarudii, F.S., Davydova, V.A., Spirikhin, L.V., Baikova, I.P., Galin, F.Z., Tolstikov, G.A., and Poroikov, V.V., Russ. J. Bioorg. Chem., 2000, vol. 26, pp. 192–200. https://doi.org/10.1007/BF02786345

    Article  CAS  Google Scholar 

  26. Barthel, A., Stark, S., and Csuk, R., Tetrahedron, 2008, vol. 64, pp. 9225–9229.

    Article  CAS  Google Scholar 

  27. Flekhter, O.B., Boreko, E.I., Nigmatullina, L.R., Pavlova, N.I., Nikolaeva, S.N., Savinova, O.V., Eremin, V.F., Baltina, L.A., Galin, F.Z., and Tolstikov, G.A., Russ. J. Bioorg. Chem., 2003, vol. 29, pp. 296–302. https://doi.org/10.1023/A:1023948919315

    Article  CAS  Google Scholar 

  28. Flekhter, O.B., Nigmatullina, L.R., Baltina, L.A., Karachurina, L.T., Galin, F.Z., Zarudii, F.S., Tolstikov, G.A., Boreko, E.I., Pavlova, N.I., Nikolaeva, S.N., and Savinova, O.V., Khim.-Farm. Zh., 2002, vol. 36, no. 9, pp. 26–28.

    Google Scholar 

  29. Kogai, T.I., Zh. Sib. Fed. Univ., Ser. Khim., 2008, no. 1, pp. 97–104.

  30. Gel'berg, S.I. and Finkel’, E.A., Probl. Tuberk., 1959, no. 2, pp. 80–84.

  31. Togunova, A.I. and Leshchinskaya, E.N., Byull. Inst. Tuberk. Akad. Med. Nauk SSSR, 1951, no. 1, pp. 27–33.

  32. Bazhin, M.A., Vlasenko, V.S., Novikov, A.N., and Patsula, Yu.I., Diskretno-dinamicheskii analiz v otsenke immuniteta: metodicheskie rekomendatsii (Discrete-Dynamic Analysis in the Assessment of Immunity: Guidelines), Omsk: Sib. Otd. Ross. Akad. S.-Kh. Nauk, 2005.

  33. Vlasenko, V.S., Donchenko, N.A., Patsula, Yu.I., Bazhin, M.A., Ivanov, A.I., Morozova, O.V., and Dudoladova, T.S., Metody otsenki funktsional’noi aktivnosti leikotsitov pri tuberkuleze i leikoze zhivotnykh (metodicheskoe posobie) (Methods for Assessing the Functional Activity of Leukocytes in Tuberculosis and Leukemia in Animals (Methodological Guide)), Omsk, 2015.

  34. Hrycek, A., Follia Biol. (Praha), 1993, vol. 39, no. 6, pp. 304–310.

    CAS  Google Scholar 

  35. Shubich, M.G., Tsitologiya, 1974, vol. 16, no. 10, pp. 1321–1322.

    CAS  Google Scholar 

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Funding

The work was supported by the state task of the Ministry of Education to Omsk Agrarian Scientific Center, project 0797-2019-0018, “Development of new and improvement of current means and methods of diagnostics and prevention of animal chronic diseases providing effective control of epizootic processes in present-day conditions” (State registration number АААА-А19-119111500003-6).

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Authors and Affiliations

  1. P.A. Stolypin Omsk State Agricultural University, 644008, Omsk, Russia

    I. N. Koshkin

  2. Omsk Agrarian Scientific Center, 644012, Omsk, Russia

    V. S. Vlasenko

  3. Institute of Chemistry, Tyumen State University, 625003, Tyumen, Russia

    I. V. Kulakov

Authors
  1. I. N. Koshkin
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  2. V. S. Vlasenko
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  3. I. V. Kulakov
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Correspondence to V. S. Vlasenko.

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COMPLIANCE WITH ETHICAL STANDARDS

The studies with guinea pigs were performed in compliance with requirements of European Convention for the Protection of Vertebrate Animals used for Experimental and other Scientific Purposes of 18.03.1986.

Conflict of Interests

The authors notified about the absence of conflict of interest.

Additional information

Translated by E. Shirokova

Abbreviations: BCG, bacillus Calmette–Guérin; LCP ACC, average cytochemical coefficient of lysosomal cationic proteins; MPO ACC, average cytochemical coefficient of myeloperoxidase, NBT test, nitroblue tetrazolium test.

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Koshkin, I.N., Vlasenko, V.S. & Kulakov, I.V. The Effect of Experimental BCG Antigen–Betulin-Derived Conjugates on the Guinea Pig Immunological Response. Russ J Bioorg Chem 47, 837–844 (2021). https://doi.org/10.1134/S1068162021040142

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