TY - JOUR

T1 - УСИЛЕНИЕ СПЕЦИФИЧЕСКОГО Т-КЛЕТОЧНОГО ИММУННОГО ОТВЕТА ПРИ ИММОБИЛИЗАЦИИ АНТИГЕНА НА МИКРО- И НАНОЧАСТИЦАХ

AU - Sakhabeev, Rodion G.

AU - Polyakov, D. S.

AU - Goshina, A. D.

AU - Vishnya, A. A.

AU - Kudryavtsev, I. V.

AU - Sinitsyna, E. S.

AU - Korzhikov-Vlakh, V.

AU - Tennikova, T. B.

AU - Shavlovsky, M. M.

N1 - Funding Information: Исследование выполнено при финансовой поддержке гранта РНФ № 19-73-10045. The study was funded by Russian Science Foundation Grant No. 19-73-10045. Publisher Copyright: © 2021 Saint Petersburg Pasteur Institute. All rights reserved.

PY - 2021/9/20

Y1 - 2021/9/20

N2 - The current study was a part of the project on generating viral particle traps occurring due to covalent immobilization on the interface of recombinant virus-specific polymer-based nano- and microparticles. It is assumed that protein-particle conjugates could be able to bind virions followed by engulfment by immune cells. The study was aimed to examine the effect of polylactic acid (PLA) and PLA block-copolymer with polyethylene glycol (PLA-PEG)-based micro- and nanoparticles on the cellular immune response against polymeric particle-bound antigen. Materials and methods. A recombinant chimeric protein beta-2-microglobulin - green fluorescent protein (β2M-sfGFP) was obtained by affine chromatography. The recombinant protein was immobilized onto the polymer particles, which were further used for mice immunization. Female F1 hybrid mice (CBA x C57BL) in experimental and control groups consisted of 4-6-month-old 15 animals (weighted 20-25 g). Intracellular cytokine staining was used to evaluate the cellular immune response. Results and discussion. It was shown that the nanoparticles of PLA block-copolymer with polyethylene glycol (PLA-PEG) were able to bind 10 microgram protein per 1 mg polymer. The polylactic acid nanoparticles were able to bind 2,3 microgram protein per 1 mg polymer. In experiment, mice in group 1 were immunized with 100 nm PLA-PEG particle-β2M-sfGFP conjugate, in group 2 - with same particles together with soluble β2M-sfGFP. In group 3, mice were immunized with 1400 nm PLA particles-β2M-sfGFP conjugate, and in group 4 - with same particles together with soluble protein. The spleens isolated 2 weeks after the four-time intraperitoneal immunization. Comparison of immune response between groups was assessed by nonparametric Kruskal-Wallis criterion with Tukey correction. It was shown that the number of antigen-specific CD4+ T cells produced to model protein was significantly higher after immunization with particle-β2M-sfGFP conjugate, as compared to control groups, wherein immunization was performed with a mixture of protein and unmodified particles (p < 0.001). It was found that the number of antigen-specific CD8+ T cells formed against β2m-sfGFP did not differ between all groups examined.

AB - The current study was a part of the project on generating viral particle traps occurring due to covalent immobilization on the interface of recombinant virus-specific polymer-based nano- and microparticles. It is assumed that protein-particle conjugates could be able to bind virions followed by engulfment by immune cells. The study was aimed to examine the effect of polylactic acid (PLA) and PLA block-copolymer with polyethylene glycol (PLA-PEG)-based micro- and nanoparticles on the cellular immune response against polymeric particle-bound antigen. Materials and methods. A recombinant chimeric protein beta-2-microglobulin - green fluorescent protein (β2M-sfGFP) was obtained by affine chromatography. The recombinant protein was immobilized onto the polymer particles, which were further used for mice immunization. Female F1 hybrid mice (CBA x C57BL) in experimental and control groups consisted of 4-6-month-old 15 animals (weighted 20-25 g). Intracellular cytokine staining was used to evaluate the cellular immune response. Results and discussion. It was shown that the nanoparticles of PLA block-copolymer with polyethylene glycol (PLA-PEG) were able to bind 10 microgram protein per 1 mg polymer. The polylactic acid nanoparticles were able to bind 2,3 microgram protein per 1 mg polymer. In experiment, mice in group 1 were immunized with 100 nm PLA-PEG particle-β2M-sfGFP conjugate, in group 2 - with same particles together with soluble β2M-sfGFP. In group 3, mice were immunized with 1400 nm PLA particles-β2M-sfGFP conjugate, and in group 4 - with same particles together with soluble protein. The spleens isolated 2 weeks after the four-time intraperitoneal immunization. Comparison of immune response between groups was assessed by nonparametric Kruskal-Wallis criterion with Tukey correction. It was shown that the number of antigen-specific CD4+ T cells produced to model protein was significantly higher after immunization with particle-β2M-sfGFP conjugate, as compared to control groups, wherein immunization was performed with a mixture of protein and unmodified particles (p < 0.001). It was found that the number of antigen-specific CD8+ T cells formed against β2m-sfGFP did not differ between all groups examined.

KW - Green fluorescent protein

KW - PLA-based microparticles

KW - PLA-PEG-based nanoparticles

KW - T-cell immune response

KW - Virus “traps”

KW - PLA-PEG-based nanoparticles

KW - PLA-based microparticles

KW - T-cell immune response

KW - green fluorescent protein

KW - virus "traps"

KW - Green fluorescent protein

KW - Virus “traps”

UR - http://www.scopus.com/inward/record.url?scp=85116610409&partnerID=8YFLogxK

UR - https://www.mendeley.com/catalogue/e83bc1b3-5edd-31e5-9e17-f3d8404c0989/

U2 - 10.15789/2220-7619-ETS-1374

DO - 10.15789/2220-7619-ETS-1374

M3 - статья

AN - SCOPUS:85116610409

VL - 11

SP - 777

EP - 783

JO - Russian Journal of Infection and Immunity

JF - Russian Journal of Infection and Immunity

SN - 2220-7619

IS - 4

ER -