Cargando…

Immunogenicity and Protective Efficacy of Influenza A DNA Vaccines Encoding Artificial Antigens Based on Conservative Hemagglutinin Stem Region and M2 Protein in Mice

Background: Development of a universal vaccine capable to induce antibody responses against a broad range of influenza virus strains attracts growing attention. Hemagglutinin stem and the exposed fragment of influenza virus M2 protein are promising targets for induction of cross-protective humoral a...

Descripción completa

Detalles Bibliográficos
Autores principales: Bazhan, Sergei, Antonets, Denis, Starostina, Ekaterina, Ilyicheva, Tatyana, Kaplina, Olga, Marchenko, Vasiliy, Durymanov, Alexander, Oreshkova, Svetlana, Karpenko, Larisa
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2020
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7565880/
https://www.ncbi.nlm.nih.gov/pubmed/32784907
http://dx.doi.org/10.3390/vaccines8030448
_version_ 1783596030207459328
author Bazhan, Sergei
Antonets, Denis
Starostina, Ekaterina
Ilyicheva, Tatyana
Kaplina, Olga
Marchenko, Vasiliy
Durymanov, Alexander
Oreshkova, Svetlana
Karpenko, Larisa
author_facet Bazhan, Sergei
Antonets, Denis
Starostina, Ekaterina
Ilyicheva, Tatyana
Kaplina, Olga
Marchenko, Vasiliy
Durymanov, Alexander
Oreshkova, Svetlana
Karpenko, Larisa
author_sort Bazhan, Sergei
collection PubMed
description Background: Development of a universal vaccine capable to induce antibody responses against a broad range of influenza virus strains attracts growing attention. Hemagglutinin stem and the exposed fragment of influenza virus M2 protein are promising targets for induction of cross-protective humoral and cell-mediated response, since they contain conservative epitopes capable to induce antibodies and cytotoxic T lymphocytes (CTLs) to a wide range of influenza virus subtypes. Methods: In this study, we generated DNA vaccine constructs encoding artificial antigens AgH1, AgH3, and AgM2 designed on the basis of conservative hemagglutinin stem fragments of two influenza A virus subtypes, H1N1 and H3N2, and conservative M2 protein, and evaluate their immunogenicity and protective efficacy. To obtain DNA vaccine constructs, genes encoding the designed antigens were cloned into a pcDNA3.1 vector. Expression of the target genes in 293T cells transfected with DNA vaccine constructs has been confirmed by synthesis of specific mRNA. Results: Immunization of BALB/c mice with DNA vaccines encoding these antigens was shown to evoke humoral and T-cell immune responses as well as a moderated statistically significant cross-protective effect against two heterologous viruses A/California/4/2009 (H1N1pdm09) and A/Aichi/2/68 (H3N2). Conclusions: The results demonstrate a potential approach to creating a universal influenza vaccine based on artificial antigens.
format Online
Article
Text
id pubmed-7565880
institution National Center for Biotechnology Information
language English
publishDate 2020
publisher MDPI
record_format MEDLINE/PubMed
spelling pubmed-75658802020-10-26 Immunogenicity and Protective Efficacy of Influenza A DNA Vaccines Encoding Artificial Antigens Based on Conservative Hemagglutinin Stem Region and M2 Protein in Mice Bazhan, Sergei Antonets, Denis Starostina, Ekaterina Ilyicheva, Tatyana Kaplina, Olga Marchenko, Vasiliy Durymanov, Alexander Oreshkova, Svetlana Karpenko, Larisa Vaccines (Basel) Article Background: Development of a universal vaccine capable to induce antibody responses against a broad range of influenza virus strains attracts growing attention. Hemagglutinin stem and the exposed fragment of influenza virus M2 protein are promising targets for induction of cross-protective humoral and cell-mediated response, since they contain conservative epitopes capable to induce antibodies and cytotoxic T lymphocytes (CTLs) to a wide range of influenza virus subtypes. Methods: In this study, we generated DNA vaccine constructs encoding artificial antigens AgH1, AgH3, and AgM2 designed on the basis of conservative hemagglutinin stem fragments of two influenza A virus subtypes, H1N1 and H3N2, and conservative M2 protein, and evaluate their immunogenicity and protective efficacy. To obtain DNA vaccine constructs, genes encoding the designed antigens were cloned into a pcDNA3.1 vector. Expression of the target genes in 293T cells transfected with DNA vaccine constructs has been confirmed by synthesis of specific mRNA. Results: Immunization of BALB/c mice with DNA vaccines encoding these antigens was shown to evoke humoral and T-cell immune responses as well as a moderated statistically significant cross-protective effect against two heterologous viruses A/California/4/2009 (H1N1pdm09) and A/Aichi/2/68 (H3N2). Conclusions: The results demonstrate a potential approach to creating a universal influenza vaccine based on artificial antigens. MDPI 2020-08-09 /pmc/articles/PMC7565880/ /pubmed/32784907 http://dx.doi.org/10.3390/vaccines8030448 Text en © 2020 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (http://creativecommons.org/licenses/by/4.0/).
spellingShingle Article
Bazhan, Sergei
Antonets, Denis
Starostina, Ekaterina
Ilyicheva, Tatyana
Kaplina, Olga
Marchenko, Vasiliy
Durymanov, Alexander
Oreshkova, Svetlana
Karpenko, Larisa
Immunogenicity and Protective Efficacy of Influenza A DNA Vaccines Encoding Artificial Antigens Based on Conservative Hemagglutinin Stem Region and M2 Protein in Mice
title Immunogenicity and Protective Efficacy of Influenza A DNA Vaccines Encoding Artificial Antigens Based on Conservative Hemagglutinin Stem Region and M2 Protein in Mice
title_full Immunogenicity and Protective Efficacy of Influenza A DNA Vaccines Encoding Artificial Antigens Based on Conservative Hemagglutinin Stem Region and M2 Protein in Mice
title_fullStr Immunogenicity and Protective Efficacy of Influenza A DNA Vaccines Encoding Artificial Antigens Based on Conservative Hemagglutinin Stem Region and M2 Protein in Mice
title_full_unstemmed Immunogenicity and Protective Efficacy of Influenza A DNA Vaccines Encoding Artificial Antigens Based on Conservative Hemagglutinin Stem Region and M2 Protein in Mice
title_short Immunogenicity and Protective Efficacy of Influenza A DNA Vaccines Encoding Artificial Antigens Based on Conservative Hemagglutinin Stem Region and M2 Protein in Mice
title_sort immunogenicity and protective efficacy of influenza a dna vaccines encoding artificial antigens based on conservative hemagglutinin stem region and m2 protein in mice
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7565880/
https://www.ncbi.nlm.nih.gov/pubmed/32784907
http://dx.doi.org/10.3390/vaccines8030448
work_keys_str_mv AT bazhansergei immunogenicityandprotectiveefficacyofinfluenzaadnavaccinesencodingartificialantigensbasedonconservativehemagglutininstemregionandm2proteininmice
AT antonetsdenis immunogenicityandprotectiveefficacyofinfluenzaadnavaccinesencodingartificialantigensbasedonconservativehemagglutininstemregionandm2proteininmice
AT starostinaekaterina immunogenicityandprotectiveefficacyofinfluenzaadnavaccinesencodingartificialantigensbasedonconservativehemagglutininstemregionandm2proteininmice
AT ilyichevatatyana immunogenicityandprotectiveefficacyofinfluenzaadnavaccinesencodingartificialantigensbasedonconservativehemagglutininstemregionandm2proteininmice
AT kaplinaolga immunogenicityandprotectiveefficacyofinfluenzaadnavaccinesencodingartificialantigensbasedonconservativehemagglutininstemregionandm2proteininmice
AT marchenkovasiliy immunogenicityandprotectiveefficacyofinfluenzaadnavaccinesencodingartificialantigensbasedonconservativehemagglutininstemregionandm2proteininmice
AT durymanovalexander immunogenicityandprotectiveefficacyofinfluenzaadnavaccinesencodingartificialantigensbasedonconservativehemagglutininstemregionandm2proteininmice
AT oreshkovasvetlana immunogenicityandprotectiveefficacyofinfluenzaadnavaccinesencodingartificialantigensbasedonconservativehemagglutininstemregionandm2proteininmice
AT karpenkolarisa immunogenicityandprotectiveefficacyofinfluenzaadnavaccinesencodingartificialantigensbasedonconservativehemagglutininstemregionandm2proteininmice