Nanoparticles Carrying Conserved Regions of Influenza A Hemagglutinin, Nucleoprotein, and M2 Protein Elicit a Strong Humoral and T Cell Immune Response and Protect Animals from Infection
Current influenza vaccines are mainly strain-specific and have limited efficacy in preventing new influenza A strains. Efficient control of infection can potentially be achieved through the development of broad-spectrum vaccines based on conserved antigens. A combination of several such antigens, in...
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MDPI AG
2023-09-01
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| author | Anna A. Zykova Elena A. Blokhina Liudmila A. Stepanova Marina A. Shuklina Olga O. Ozhereleva Liudmila M. Tsybalova Victor V. Kuprianov Nikolai V. Ravin |
| author_facet | Anna A. Zykova Elena A. Blokhina Liudmila A. Stepanova Marina A. Shuklina Olga O. Ozhereleva Liudmila M. Tsybalova Victor V. Kuprianov Nikolai V. Ravin |
| author_sort | Anna A. Zykova |
| collection | DOAJ |
| description | Current influenza vaccines are mainly strain-specific and have limited efficacy in preventing new influenza A strains. Efficient control of infection can potentially be achieved through the development of broad-spectrum vaccines based on conserved antigens. A combination of several such antigens, including the conserved region of the second subunit of the hemagglutinin (HA2), the extracellular domain of the M2 protein (M2e), and epitopes of nucleoprotein (NP), which together can elicit an antibody- and cell-mediated immune response, would be preferred for vaccine development. In this study, we obtained recombinant virus-like particles formed by an artificial self-assembling peptide (SAP) carrying two epitopes from NP, tandem copies of M2e and HA2 peptides, along with a T helper Pan DR-binding epitope (PADRE). Fusion proteins expressed in <i>Escherichia coli</i> self-assembled in vitro into spherical particles with a size of 15–35 nm. Immunization of mice with these particles induced strong humoral immune response against M2e and the entire virus, and lead to the formation of cytokine-secreting antigen-specific CD4+ and CD8+ effector memory T cells. Immunization provided high protection of mice against the lethal challenge with the influenza A virus. Our results show that SAP-based nanoparticles carrying conserved peptides from M2, HA, and NP proteins of the influenza A virus, as well as T helper epitope PADRE, can be used for the development of universal flu vaccines. |
| first_indexed | 2024-03-10T22:25:29Z |
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| id | doaj.art-c56acac6d59644ae85173d9fa7d8c895 |
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| language | English |
| last_indexed | 2024-03-10T22:25:29Z |
| publishDate | 2023-09-01 |
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| series | Molecules |
| spelling | doaj.art-c56acac6d59644ae85173d9fa7d8c8952023-11-19T12:07:25ZengMDPI AGMolecules1420-30492023-09-012818644110.3390/molecules28186441Nanoparticles Carrying Conserved Regions of Influenza A Hemagglutinin, Nucleoprotein, and M2 Protein Elicit a Strong Humoral and T Cell Immune Response and Protect Animals from InfectionAnna A. Zykova0Elena A. Blokhina1Liudmila A. Stepanova2Marina A. Shuklina3Olga O. Ozhereleva4Liudmila M. Tsybalova5Victor V. Kuprianov6Nikolai V. Ravin7Institute of Bioengineering, Research Center of Biotechnology of the Russian Academy of Sciences, Moscow 119071, RussiaInstitute of Bioengineering, Research Center of Biotechnology of the Russian Academy of Sciences, Moscow 119071, RussiaSmorodintsev Research Institute of Influenza, Russian Ministry of Health, St. Petersburg 197376, RussiaSmorodintsev Research Institute of Influenza, Russian Ministry of Health, St. Petersburg 197376, RussiaSmorodintsev Research Institute of Influenza, Russian Ministry of Health, St. Petersburg 197376, RussiaSmorodintsev Research Institute of Influenza, Russian Ministry of Health, St. Petersburg 197376, RussiaInstitute of Bioengineering, Research Center of Biotechnology of the Russian Academy of Sciences, Moscow 119071, RussiaInstitute of Bioengineering, Research Center of Biotechnology of the Russian Academy of Sciences, Moscow 119071, RussiaCurrent influenza vaccines are mainly strain-specific and have limited efficacy in preventing new influenza A strains. Efficient control of infection can potentially be achieved through the development of broad-spectrum vaccines based on conserved antigens. A combination of several such antigens, including the conserved region of the second subunit of the hemagglutinin (HA2), the extracellular domain of the M2 protein (M2e), and epitopes of nucleoprotein (NP), which together can elicit an antibody- and cell-mediated immune response, would be preferred for vaccine development. In this study, we obtained recombinant virus-like particles formed by an artificial self-assembling peptide (SAP) carrying two epitopes from NP, tandem copies of M2e and HA2 peptides, along with a T helper Pan DR-binding epitope (PADRE). Fusion proteins expressed in <i>Escherichia coli</i> self-assembled in vitro into spherical particles with a size of 15–35 nm. Immunization of mice with these particles induced strong humoral immune response against M2e and the entire virus, and lead to the formation of cytokine-secreting antigen-specific CD4+ and CD8+ effector memory T cells. Immunization provided high protection of mice against the lethal challenge with the influenza A virus. Our results show that SAP-based nanoparticles carrying conserved peptides from M2, HA, and NP proteins of the influenza A virus, as well as T helper epitope PADRE, can be used for the development of universal flu vaccines.https://www.mdpi.com/1420-3049/28/18/6441nanoparticleself-assembling peptideinfluenza AM2e peptidehemagglutininimmune response |
| spellingShingle | Anna A. Zykova Elena A. Blokhina Liudmila A. Stepanova Marina A. Shuklina Olga O. Ozhereleva Liudmila M. Tsybalova Victor V. Kuprianov Nikolai V. Ravin Nanoparticles Carrying Conserved Regions of Influenza A Hemagglutinin, Nucleoprotein, and M2 Protein Elicit a Strong Humoral and T Cell Immune Response and Protect Animals from Infection Molecules nanoparticle self-assembling peptide influenza A M2e peptide hemagglutinin immune response |
| title | Nanoparticles Carrying Conserved Regions of Influenza A Hemagglutinin, Nucleoprotein, and M2 Protein Elicit a Strong Humoral and T Cell Immune Response and Protect Animals from Infection |
| title_full | Nanoparticles Carrying Conserved Regions of Influenza A Hemagglutinin, Nucleoprotein, and M2 Protein Elicit a Strong Humoral and T Cell Immune Response and Protect Animals from Infection |
| title_fullStr | Nanoparticles Carrying Conserved Regions of Influenza A Hemagglutinin, Nucleoprotein, and M2 Protein Elicit a Strong Humoral and T Cell Immune Response and Protect Animals from Infection |
| title_full_unstemmed | Nanoparticles Carrying Conserved Regions of Influenza A Hemagglutinin, Nucleoprotein, and M2 Protein Elicit a Strong Humoral and T Cell Immune Response and Protect Animals from Infection |
| title_short | Nanoparticles Carrying Conserved Regions of Influenza A Hemagglutinin, Nucleoprotein, and M2 Protein Elicit a Strong Humoral and T Cell Immune Response and Protect Animals from Infection |
| title_sort | nanoparticles carrying conserved regions of influenza a hemagglutinin nucleoprotein and m2 protein elicit a strong humoral and t cell immune response and protect animals from infection |
| topic | nanoparticle self-assembling peptide influenza A M2e peptide hemagglutinin immune response |
| url | https://www.mdpi.com/1420-3049/28/18/6441 |
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