Результаты исследований: Научные публикации в периодических изданиях › статья › Рецензирование
In silico design of influenza a virus artificial epitope-based T-cell antigens and the evaluation of their immunogenicity in mice. / Bazhan, Sergei I.; Antonets, Denis V.; Starostina, Ekaterina V. и др.
в: Journal of Biomolecular Structure and Dynamics, Том 40, № 7, 2022, стр. 3196-3212.Результаты исследований: Научные публикации в периодических изданиях › статья › Рецензирование
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TY - JOUR
T1 - In silico design of influenza a virus artificial epitope-based T-cell antigens and the evaluation of their immunogenicity in mice
AU - Bazhan, Sergei I.
AU - Antonets, Denis V.
AU - Starostina, Ekaterina V.
AU - Ilyicheva, Tatyana N.
AU - Kaplina, Olga N.
AU - Marchenko, Vasiliy Yu
AU - Volkova, Olga Yu
AU - Bakulina, Anastasiya Yu
AU - Karpenko, Larisa I.
N1 - Funding Information: The study was funded by the Russian Science Foundation Grant [15-15-00047] and partly by the state assignment of FBRI SRC VB ?Vector?, Rospotrebnadzor Publisher Copyright: © 2020 Informa UK Limited, trading as Taylor & Francis Group.
PY - 2022
Y1 - 2022
N2 - The polyepitope strategy is promising approach for successfully creating a broadly protective flu vaccine, which targets T-lymphocytes (both CD4+ and CD8+) to recognise the most conserved epitopes of viral proteins. In this study, we employed a computer-aided approach to develop several artificial antigens potentially capable of evoking immune responses to different virus subtypes. These antigens included conservative T-cell epitopes of different influenza A virus proteins. To design epitope-based antigens we used experimentally verified information regarding influenza virus T-cell epitopes from the Immune Epitope Database (IEDB) (http://www.iedb.org). We constructed two “human” and two “murine” variants of polyepitope antigens. Amino acid sequences of target polyepitope antigens were designed using our original TEpredict/PolyCTLDesigner software. Immunogenic and protective features of DNA constructs encoding “murine” target T-cell immunogens were studied in BALB/c mice. We showed that mice groups immunised with a combination of computer-generated “murine” DNA immunogens had a 37.5% survival rate after receiving a lethal dose of either A/California/4/2009 (H1N1) virus or A/Aichi/2/68 (H3N2) virus, while immunisation with live flu H1N1 and H3N2 vaccine strains provided protection against homologous viruses and failed to protect against heterologous viruses. These results demonstrate that mechanisms of cross-protective immunity may be associated with the stimulation of specific T-cell responses. This study demonstrates that our computer-aided approach may be successfully used for rational designing artificial polyepitope antigens capable of inducing virus-specific T-lymphocyte responses and providing partial protection against two different influenza virus subtypes. Communicated by Ramaswamy H. Sarma.
AB - The polyepitope strategy is promising approach for successfully creating a broadly protective flu vaccine, which targets T-lymphocytes (both CD4+ and CD8+) to recognise the most conserved epitopes of viral proteins. In this study, we employed a computer-aided approach to develop several artificial antigens potentially capable of evoking immune responses to different virus subtypes. These antigens included conservative T-cell epitopes of different influenza A virus proteins. To design epitope-based antigens we used experimentally verified information regarding influenza virus T-cell epitopes from the Immune Epitope Database (IEDB) (http://www.iedb.org). We constructed two “human” and two “murine” variants of polyepitope antigens. Amino acid sequences of target polyepitope antigens were designed using our original TEpredict/PolyCTLDesigner software. Immunogenic and protective features of DNA constructs encoding “murine” target T-cell immunogens were studied in BALB/c mice. We showed that mice groups immunised with a combination of computer-generated “murine” DNA immunogens had a 37.5% survival rate after receiving a lethal dose of either A/California/4/2009 (H1N1) virus or A/Aichi/2/68 (H3N2) virus, while immunisation with live flu H1N1 and H3N2 vaccine strains provided protection against homologous viruses and failed to protect against heterologous viruses. These results demonstrate that mechanisms of cross-protective immunity may be associated with the stimulation of specific T-cell responses. This study demonstrates that our computer-aided approach may be successfully used for rational designing artificial polyepitope antigens capable of inducing virus-specific T-lymphocyte responses and providing partial protection against two different influenza virus subtypes. Communicated by Ramaswamy H. Sarma.
KW - DNA vaccine
KW - immunogenicity
KW - In silico design
KW - influenza virus
KW - T-cell epitope-based antigens
KW - IMMUNITY
KW - PEPTIDE BINDING
KW - MOTIF
KW - PROTECTIVE EFFICACY
KW - PREDICTION
KW - MHC CLASS-I
KW - NANOPARTICLES
KW - DNA VACCINES
KW - FLANKING REGION
KW - RATIONAL DESIGN
UR - http://www.scopus.com/inward/record.url?scp=85096573337&partnerID=8YFLogxK
U2 - 10.1080/07391102.2020.1845978
DO - 10.1080/07391102.2020.1845978
M3 - Article
C2 - 33222632
AN - SCOPUS:85096573337
VL - 40
SP - 3196
EP - 3212
JO - Journal of Biomolecular Structure and Dynamics
JF - Journal of Biomolecular Structure and Dynamics
SN - 0739-1102
IS - 7
ER -
ID: 26136551