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...
| Main Authors: | , , , , , , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
MDPI AG
2020-08-01
|
| Series: | Vaccines |
| Subjects: | |
| Online Access: | https://www.mdpi.com/2076-393X/8/3/448 |
| _version_ | 1797559325779034112 |
|---|---|
| author | Sergei Bazhan Denis Antonets Ekaterina Starostina Tatyana Ilyicheva Olga Kaplina Vasiliy Marchenko Alexander Durymanov Svetlana Oreshkova Larisa Karpenko |
| author_facet | Sergei Bazhan Denis Antonets Ekaterina Starostina Tatyana Ilyicheva Olga Kaplina Vasiliy Marchenko Alexander Durymanov Svetlana Oreshkova Larisa Karpenko |
| author_sort | Sergei Bazhan |
| collection | DOAJ |
| 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. |
| first_indexed | 2024-03-10T17:43:43Z |
| format | Article |
| id | doaj.art-564333e9baae4cf4858bbf0dd4d26632 |
| institution | Directory Open Access Journal |
| issn | 2076-393X |
| language | English |
| last_indexed | 2024-03-10T17:43:43Z |
| publishDate | 2020-08-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Vaccines |
| spelling | doaj.art-564333e9baae4cf4858bbf0dd4d266322023-11-20T09:35:56ZengMDPI AGVaccines2076-393X2020-08-018344810.3390/vaccines8030448Immunogenicity and Protective Efficacy of Influenza A DNA Vaccines Encoding Artificial Antigens Based on Conservative Hemagglutinin Stem Region and M2 Protein in MiceSergei Bazhan0Denis Antonets1Ekaterina Starostina2Tatyana Ilyicheva3Olga Kaplina4Vasiliy Marchenko5Alexander Durymanov6Svetlana Oreshkova7Larisa Karpenko8Theoretical Department, State Research Center of Virology and Biotechnology “Vector”, Koltsovo 630559, Novosibirsk Region, RussiaTheoretical Department, State Research Center of Virology and Biotechnology “Vector”, Koltsovo 630559, Novosibirsk Region, RussiaBioengineering Department, State Research Center of Virology and Biotechnology “Vector”, Koltsovo 630559, Novosibirsk Region, RussiaDepartment of Zoonotic Infections and Influenza, State Research Center of Virology and Biotechnology “Vector”, Koltsovo 630559, Novosibirsk Region, RussiaBioengineering Department, State Research Center of Virology and Biotechnology “Vector”, Koltsovo 630559, Novosibirsk Region, RussiaDepartment of Zoonotic Infections and Influenza, State Research Center of Virology and Biotechnology “Vector”, Koltsovo 630559, Novosibirsk Region, RussiaDepartment of Zoonotic Infections and Influenza, State Research Center of Virology and Biotechnology “Vector”, Koltsovo 630559, Novosibirsk Region, RussiaBioengineering Department, State Research Center of Virology and Biotechnology “Vector”, Koltsovo 630559, Novosibirsk Region, RussiaBioengineering Department, State Research Center of Virology and Biotechnology “Vector”, Koltsovo 630559, Novosibirsk Region, RussiaBackground: 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.https://www.mdpi.com/2076-393X/8/3/448influenza virusDNA-vaccine constructsartificial polyepitope T-cell immunogenshemagglutinin stem regionM2 proteincross-protective influenza immunity |
| spellingShingle | Sergei Bazhan Denis Antonets Ekaterina Starostina Tatyana Ilyicheva Olga Kaplina Vasiliy Marchenko Alexander Durymanov Svetlana Oreshkova Larisa Karpenko Immunogenicity and Protective Efficacy of Influenza A DNA Vaccines Encoding Artificial Antigens Based on Conservative Hemagglutinin Stem Region and M2 Protein in Mice Vaccines influenza virus DNA-vaccine constructs artificial polyepitope T-cell immunogens hemagglutinin stem region M2 protein cross-protective influenza immunity |
| 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 | influenza virus DNA-vaccine constructs artificial polyepitope T-cell immunogens hemagglutinin stem region M2 protein cross-protective influenza immunity |
| url | https://www.mdpi.com/2076-393X/8/3/448 |
| work_keys_str_mv | AT sergeibazhan immunogenicityandprotectiveefficacyofinfluenzaadnavaccinesencodingartificialantigensbasedonconservativehemagglutininstemregionandm2proteininmice AT denisantonets immunogenicityandprotectiveefficacyofinfluenzaadnavaccinesencodingartificialantigensbasedonconservativehemagglutininstemregionandm2proteininmice AT ekaterinastarostina immunogenicityandprotectiveefficacyofinfluenzaadnavaccinesencodingartificialantigensbasedonconservativehemagglutininstemregionandm2proteininmice AT tatyanailyicheva immunogenicityandprotectiveefficacyofinfluenzaadnavaccinesencodingartificialantigensbasedonconservativehemagglutininstemregionandm2proteininmice AT olgakaplina immunogenicityandprotectiveefficacyofinfluenzaadnavaccinesencodingartificialantigensbasedonconservativehemagglutininstemregionandm2proteininmice AT vasiliymarchenko immunogenicityandprotectiveefficacyofinfluenzaadnavaccinesencodingartificialantigensbasedonconservativehemagglutininstemregionandm2proteininmice AT alexanderdurymanov immunogenicityandprotectiveefficacyofinfluenzaadnavaccinesencodingartificialantigensbasedonconservativehemagglutininstemregionandm2proteininmice AT svetlanaoreshkova immunogenicityandprotectiveefficacyofinfluenzaadnavaccinesencodingartificialantigensbasedonconservativehemagglutininstemregionandm2proteininmice AT larisakarpenko immunogenicityandprotectiveefficacyofinfluenzaadnavaccinesencodingartificialantigensbasedonconservativehemagglutininstemregionandm2proteininmice |