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 -