J Biomol Struct Dyn . In silico design of influenza a virus artificial epitope-based T-cell antigens and the evaluation of their immunogenicity in mice

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J Biomol Struct Dyn


. 2020 Nov 23;1-17.
doi: 10.1080/07391102.2020.1845978. Online ahead of print.
In silico design of influenza a virus artificial epitope-based T-cell antigens and the evaluation of their immunogenicity in mice


Sergei I Bazhan ¹ , Denis V Antonets ¹ , Ekaterina V Starostina ² , Tatyana N Ilyicheva ³ , Olga N Kaplina ² , Vasiliy Yu Marchenko ³ , Olga Yu Volkova ⁴ , Anastasiya Yu Bakulina ^{1 5} , Larisa I Karpenko ²



Affiliations

• PMID: 33222632
• DOI: 10.1080/07391102.2020.1845978

Abstract

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.

Keywords: DNA vaccine; In silico design; T-cell epitope-based antigens; immunogenicity; influenza virus.