Enhancing the specific T cell immune response against micro- and nanoparticle immobilized antigen
- Authors: Sakhabeev R.G.1, Polyakov D.S.1, Goshina A.D.2, Vishnya A.A.3, Kudryavtsev I.V.1, Sinitcina E.S.4,5, Korzhikov-Vlakh V.А.4, Tennikova T.B.2,4, Shavlovsky M.M.1,6
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Affiliations:
- Institute of Experimental Medicine
- St. Petersburg State University
- Herzen State Pedagogical University of Russia
- Institute of Chemistry, St. Petersburg State University
- Institute of Macromolecular Compounds of the Russian Academy of Sciences
- Pavlov First St. Petersburg State Medical University
- Issue: Vol 11, No 4 (2021)
- Pages: 777-783
- Section: SHORT COMMUNICATIONS
- Submitted: 03.02.2020
- Accepted: 14.09.2020
- Published: 23.10.2020
- URL: https://iimmun.ru/iimm/article/view/1374
- DOI: https://doi.org/10.15789/2220-7619-ETS-1374
- ID: 1374
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Full Text
Abstract
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.
About the authors
R. G. Sakhabeev
Institute of Experimental Medicine
Author for correspondence.
Email: helm505@mail.ru
ORCID iD: 0000-0002-4367-4924
Rodion G. Sakhabeev, Junior Researcher, Department of Molecular Genetics
197376, St. Petersburg, Academician Pavlov str., 12
Phone: +7 953 152-68-07
РоссияD. S. Polyakov
Institute of Experimental Medicine
Email: ravendoctor@mail.ru
PhD (Medicine), Researcher, Department of Molecular Genetics
St. Petersburg
A. D. Goshina
St. Petersburg State University
Email: arina8goshina@gmail.com
4th-year Student
St. Petersburg
A. A. Vishnya
Herzen State Pedagogical University of Russia
Email: tlou000@yandex.ru
2th-year Master Student
St. Petersburg
I. V. Kudryavtsev
Institute of Experimental Medicine
Email: igorek1981@yandex.ru
PhD (Biology), Head of the Laboratory of Immunoregulation, Department of Immunology
St. Petersburg
E. S. Sinitcina
Institute of Chemistry, St. Petersburg State University; Institute of Macromolecular Compounds of the Russian Academy of Sciences
Email: kat_sinitsyna@mail.ru
PhD (Chemistry), Senior Researcher, Interdisciplinary Laboratory of Biomedical Chemistry; Researcher, Laboratory of Polymer Sorbents and Carriers for Biotechnology
St. Petersburg
V. А. Korzhikov-Vlakh
Institute of Chemistry, St. Petersburg State University
Email: v_korzhikov@mail.ru
PhD (Chemistry), Associate Professor, Interdisciplinary Laboratory of Biomedical Chemistry
St. Petersburg
T. B. Tennikova
St. Petersburg State University; Institute of Chemistry, St. Petersburg State University
Email: tennikova@mail.ru
PhD, MD (Chemistry), Professor, Leading Researcher and Head of the Interdisciplinary Laboratory of Biomedical Chemistry
St. Petersburg
M. M. Shavlovsky
Institute of Experimental Medicine; Pavlov First St. Petersburg State Medical University
Email: mmsch@rambler.ru
PhD, MD (Medicine), Head of the Molecular Genetics Laboratory; Professor
St. Petersburg
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