Recombinant vaccine candidates with integrated adjuvants provide stimulation of an effective immune response against bacterial infections
https://doi.org/10.18705/2782-3806-2022-2-6-64-77
Abstract
The use of recombinant proteins as vaccine preparations is limited by their weak immunogenicity, which can be enhanced by the use of adjuvants, the development of which is an important and urgent problem of modern vaccinology. Significantly, adjuvants as additives to vaccine preparations are of concern to clinicians. From this point of view, the idea of including an internal adjuvant into the structure of a recombinant protein molecule is of undoubted interest. Previously, we synthesized and studied two recombinant vaccine preparations specific for S. agalactiae (Su4) and S. pneumoniae (PSPF). Each of them was a tandem of immunogenic bacterial surface proteins in combination with an additional adjuvant site. The amino acid sequence identical to flagellin acted as an internal adjuvant. In this work, we investigated the possibility of additional enhancement of the body’s immune response to immunization with recombinant Su4 and PSPF proteins due to the simultaneous administration of an external adjuvant, carboxymethylchitosan or Imject Alum.
Studies have shown that the additional introduction of these adjuvants into the composition of the vaccine preparation did not affect the immunogenicity of the Su4 and PSPF proteins, which included the internal adjuvant flagellin. The protective efficacy of the immune response to all immunization options was comparable.
Thus, the inclusion of a flagellin insert as an internal adjuvant into the composition of recombinant proteins ensures the development of the highest possible level of the immune response and its protective efficacy against the corresponding pathogens of a bacterial infection.
About the Authors
G. F. LeontievaRussian Federation
Leontieva Galina F., Cand. Sc. (Biology), Leading Researcher
Academician Pavlov str., 12, Saint Petersburg, 197022
T. A. Kramskaya
Russian Federation
Kramskaya Tatyana A., Cand. Sc. (Biology), Senior Researcher
Saint Petersburg
K. B. Grabovskaya
Russian Federation
Grabovskaya Kornelia B., Cand. Sc. (Biology), Senior Researcher
Saint Petersburg
T. V. Gupalova
Russian Federation
Gupalova Tatyana V., D.Sc. (Biology), Leading Researcher
Saint Petersburg
A. V. Dmitriev
Russian Federation
Dmitriev Alexander V., D.Sc. (Medicine), director
Saint Petersburg
A. N. Suvorov
Russian Federation
Suvorov Alexander N., D.Sc. (Medicine), Head of Department
Saint Petersburg
References
1. Christodoulides M, Jolley KA, Heckels JE. Recombinant proteins in vaccine development. Methods Mol Med. 2001;66:167–80. DOI: 10.1385/1-59259-1485:167. PMID: 21336755.
2. Suvorov A, Dukhovlinov I, Leontieva G, et al. Chimeric Protein PSPF, a Potential Vaccine for Prevention Streptococcus pneumoniae Infection January 2015Journal of Vaccines and Vaccination 06(06) DOI: 10.4172/2157-7560.1000304.
3. Laiño J, Villena J, Suvorov A, et al. Nasal immunization with recombinant chimeric pneumococcal protein and cell wall from immunobiotic bacteria improve resistance of infant mice to Streptococcus pneumoniae infection. PLoS One. 2018 Nov 5;13(11):e0206661. DOI: 10.1371/journal.pone.0206661. PMID: 30395582; PMCID: PMC6218053.
4. Hu MC, Walls MA, Stroop SD, et al. Immunogenicity of a 26-valent group A streptococcal vaccine. Infect Immun. 2002;70(4):2171–7.
5. Dale JB, Walker MJ. Update on group A streptococcal vaccine development. Curr Opin Infect Dis. 2020 Jun;33(3):244–250. DOI: 10.1097QCO.0000000000000644.
6. Shan P, Wang Z, Li J, et al. A New Nano Adjuvant of PF3 Used for an Enhanced Hepatitis B Vaccine. Front Bioeng Biotechnol. 2022 May 10;10:903424. DOI: 10.3389/fbioe.2022.903424. PMID: 35620473; PMCID: PMC9127465.
7. Guan LJ, Pei SX, Song JJ, et al. Screening immune adjuvants for an inactivated vaccine against Erysipelothrix rhusiopathiae. Front Vet Sci. 2022 Jul 26;9:922867. DOI: 10.3389/fvets.2022.922867. PMID: 35958306; PMCID: PMC9360596.
8. Kwissa M, Kasturi SP, Pulendran B. The science of adjuvants. Expert Rev Vaccines. 2007 Oct;6(5):673– 84. DOI: 10.1586/14760584.6.5.673. PMID: 17931149.
9. Petrovsky N. Comparative Safety of Vaccine Adjuvants: A Summary of Current Evidence and Future Needs. Drug Saf. 2015 Nov;38(11):1059–74. DOI: 10.1007/s40264-015-0350-4.
10. Hayashi F, Smith KD, Ozinsky A, et al. The innate immune response to bacterial flagellin is mediated by Toll-like receptor 5. Nature 2001; 410: 1099–1103.
11. Filimonova VYu, Dukhovlinov IV, Kramskaya TA, et al. Chimeric proteins based on immunogenic epitopes of surface pathogenicity factors of streptococci as a vaccine for the prevention of infection caused by group B streptococci. Academic Medical Journal, 2016, vol. 16, No. 3, 82–89. In Russian [Филимоновa В.Ю., Духовлинов И.В., Крамская Т.А. и др. Химерные белки на основе иммуногенных эпитопов поверхностных факторов патогенности стрептококков в качестве вакцины для профилактики инфекции, вызванной стрептококками группы В. Медицинский академический журнал, 2016, т. 16, № 3, 82–89.]
12. Kool M, Fierens K, Lambrecht BN. Alum adjuvant: some of the tricks of the oldest adjuvant. J Med Microbiol. 2012 Jul;61(Pt 7):927–934. DOI: 10.1099/jmm.0.038943-0.
13. RK Gupta 1 Aluminum compounds as vaccine adjuvants Adv Drug Deliv Rev 1998 Jul 6;32(3):155–172. DOI: 10.1016/s0169-409x(98)00008-8).
14. Zhao K, Han J, Zhang Y, et al. Enhancing Mu-cosal Immune Response of Newcastle Disease Virus DNA Vaccine Using N-2-Hydroxypropyl Trimethylammonium Chloride Chitosan and N,O-Carboxymethyl Chitosan Nanoparticles as Delivery Carrier. Mol Pharm. 2018 Jan 2;15(1):226–237. DOI: 10.1021/acs.molpharmaceut.7b00826. Epub 2017 Dec 6. PMID: 29172532.
15. Trinchieri G, Sher A. Cooperation of Toll-like receptor signals in innate immune defence. Nat. Rev. Immunol. 2007; 7:179–190. DOI: 10.1038/nri2038.
16. Kulikov SN, Chirkov SN, Ilyin AV. Influence of the molecular weight of chitosan on its antiviral activity in plants. Applied biochemistry and microbiology. — 2006. — T. 42. — No. 2. — S. 224–228. In Russian [Куликов С.Н., Чирков С.Н., Ильина А.В. Влияние молекулярной массы хитозана на его противовирусную активность в растениях. Прикладная биохимия и микробиология. — 2006. — Т. 42. — № 2. — С. 224–228.]
17. Makimura YY, Watanabe S, Suzuki T., et al. Chemoenzymatic synthesis and application of a sialoglycopolymer with a chitosan backbone as a potent inhibitor of human influenza virus hemagglutination. Carbohydr Res. — 2006. — Vol. 341. — P. 1803–1808.
18. Lim SH, Hudson SM. Review of chitosan and its derivatives as antimicrobial agents and their uses as textile chemicals. J. Macromol. Sci. — 2003. — Vol. 43. — N. 2. — P. 223–269.
19. Lin SB, Lin YC, Chen HH. Low molecular weight chitosan prepared with the aid of cellulase, lysozyme and chitinase: characterisation and antibacterial activity. Food Chemistry. — 2009. — Vol. 116. — N. 1. — P. 47–53.
20. Moine L, Canali MM, Porporatto C, Correa SG. Reviewing the biological activity of chitosan in the mucosa: Focus on intestinal immunity. Int J Biol Macromol. 2021 Oct 31;189:324–334. DOI: 10.1016/j.ijbiomac.2021.08.098.
Review
For citations:
Leontieva G.F., Kramskaya T.A., Grabovskaya K.B., Gupalova T.V., Dmitriev A.V., Suvorov A.N. Recombinant vaccine candidates with integrated adjuvants provide stimulation of an effective immune response against bacterial infections. Russian Journal for Personalized Medicine. 2022;2(6):64-77. (In Russ.) https://doi.org/10.18705/2782-3806-2022-2-6-64-77