| Autor: |
Shuklina, Marina, Stepanova, Liudmila, Ozhereleva, Olga, Kovaleva, Anna, Vidyaeva, Inna, Korotkov, Alexandr, Tsybalova, Liudmila |
| Předmět: |
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| Zdroj: |
Biology (2079-7737); Oct2024, Vol. 13 Issue 10, p801, 15p |
| Abstrakt: |
Simple Summary: The influenza virus is a global problem for humanity due to its high variability. Research is ongoing worldwide to develop a so-called universal vaccine to control this infection. Chimeric proteins are one of the platforms for the development of such a vaccine. Within this platform, the least variable proteins of the influenza virus are used so that the vaccine can protect against many strains. In this work, we investigated the possibility of enhancing the efficacy of a candidate vaccine protein by introducing an additional fragment of influenza virus into the construct. Antigen-specific antibody and T-cell immune responses in mice to vaccination were evaluated. Animals were challenged with a lethal dose of influenza viruses to assess the efficacy of the candidate vaccine proteins. It was found that the introduction of new conserved antigens into the construct affects the formation of antibodies to other vaccine antigens but does not affect the protective efficacy of the candidate protein. Conserved influenza virus proteins, such as the hemagglutinin stem domain (HA2), nucleoprotein (NP), and matrix protein (M), are the main targets in the development of universal influenza vaccines. Previously, we constructed a recombinant vaccine protein Flg-HA2-2-4M2ehs containing the extracellular domain of the M2 protein (M2e) and the aa76–130 sequence of the second HA subunit as target antigens. It demonstrated immunogenicity and broad protection against influenza A viruses after intranasal and parenteral administration. This study shows that CD8+ epitopes of NP, inserted into a flagellin-fused protein carrying M2e and HA2, affect the post-vaccination immune humoral response to virus antigens without reducing protection. No differences were found between the two proteins in their ability to stimulate the formation of follicular Th in the spleen, which may contribute to a long-lasting antigen-specific humoral response. The data obtained on Balb/c mice suggest that the insertion of CTL NP epitopes into the flagellin-fused protein carrying M2e and HA2 reduces the antibody response to M2e and A/H3N2. In C57Bl6 mice, this stimulates the formation of NP-specific CD8+ Tem and virus-specific mono- and multifunctional CD4+ and CD8+ Tem in the spleen and completely protects mice from influenza virus subtypes A/H1N1pdm09 and A/H3N2. [ABSTRACT FROM AUTHOR] |
| Databáze: |
Complementary Index |
| Externí odkaz: |
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