Conserved linear B-cell peptides among the influenza A viral neuraminidases enhance the cross-protective potential of inactivated whole-virion influenza vaccine
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1. | Title | Title of document | Conserved linear B-cell peptides among the influenza A viral neuraminidases enhance the cross-protective potential of inactivated whole-virion influenza vaccine |
2. | Creator | Author's name, affiliation, country | Tatiana S. Kotomina; Institute of Experimental Medicine; Россия |
2. | Creator | Author's name, affiliation, country | I. A. Sychev; Institute of Experimental Medicine; Россия |
2. | Creator | Author's name, affiliation, country | A. Ya. Rak; Institute of Experimental Medicine; Россия |
2. | Creator | Author's name, affiliation, country | P.-F. Wong; Institute of Experimental Medicine; Россия |
2. | Creator | Author's name, affiliation, country | A. V. Bazhina; Institute of Experimental Medicine; Россия |
2. | Creator | Author's name, affiliation, country | I. N. Isakova-Sivak; Institute of Experimental Medicine; Россия |
2. | Creator | Author's name, affiliation, country | L. G. Rudenko; Institute of Experimental Medicine; Россия |
3. | Subject | Discipline(s) | |
3. | Subject | Keyword(s) | influenza A virus; immune response; universal influenza vaccine; heterosubtypic immune response; antineuraminidase antibodies; linear B-cell epitopes |
4. | Description | Abstract | Introduction. Influenza is a disease caused by a widespread virus with pandemic potential. Frequently, individuals vaccinated against seasonal influenza virus are still susceptible to the disease, indicating the need to improve the immunogenic potential of existing vaccines. To assess the efficacy of influenza virus vaccines, immune response only to a single viral antigen — hemagglutinin molecule, is taken into consideration. However, according to preclinical and clinical studies, neuraminidase (NA) stimulates cross-protective immunity, which is effective against not only homologous but also drifted variants of influenza A virus. Materials and methods. In the present study, we investigated the ability of previously selected conserved linear B-cell NA epitopes (SGYSGK, SWPDGK, EECSCYPK, VELIRGRK) to enhance the immunogenicity of an inactivated whole-virion influenza vaccine based on the model strain PR8 (iPR8). BALB/c mice were injected with iPR8 in combination with one of the peptides intramuscularly three times at two-week intervals. Blood samples were collected 14 days after the last immunization, after which the mice were challenged with heterosubtypic influenza viruses H1N1pdm09 and H3N2. Results. All immunized mice showed induction of H1N1 (PR8)-specific IgG antibodies two weeks after the third immunization. The group of mice immunized with the iPR8 vaccine preparation in combination with VELIRGRK peptide showed the most pronounced induction of IgG antibodies to the H6N1 reassortant strain, the NA of which corresponds to the iPR8 virus, indicating the ability of the NA peptide to stimulate the production of NA-specific antibodies. However, the antibodies produced after immunization were not capable to inhibit the NA enzymatic activity. Despite this, mice immunized with iPR8 in combination with anti-NA peptides showed a higher survival rate after infection with heterologous virulent influenza viruses: A/California/07/09 (H1N1pdm09) and A/Philippines/2/82 (H3N2) compared to the PBS and iPR8 groups. Conclusion. Thus, the study demonstrated the immune-potentiating effect of individual peptides corresponding to conservative linear epitopes of the NA molecule in combination with a standard inactivated influenza vaccine, which made it possible to improve the protective effect of the vaccine against heterosubtypic influenza viruses. |
5. | Publisher | Organizing agency, location | SPb RAACI |
6. | Contributor | Sponsor(s) |
Ministry of Science and Higher Education of the Russian Federation (project) (FGWG-2022-0001) |
7. | Date | (DD-MM-YYYY) | 28.07.2024 |
8. | Type | Status & genre | Peer-reviewed Article |
8. | Type | Type | Short Communication |
9. | Format | File format | |
10. | Identifier | Uniform Resource Identifier | https://iimmun.ru/iimm/article/view/17742 |
10. | Identifier | Digital Object Identifier (DOI) | 10.15789/2220-7619-CLB-16932 |
11. | Source | Title; vol., no. (year) | Russian Journal of Infection and Immunity; Vol 14, No 3 (2024) |
12. | Language | English=en | ru |
13. | Relation | Supp. Files |
Figure 1. Study designs and timelines for experiment in BALB/c mice (358KB) Figure 2. Dynamics of body weight loss and survival rate of nonimmunized BALB/c mice (PBS) and BALB/c mice immunized with inactivated iPR8 vaccine individually or in combination with one of the B-cell neuraminidase peptides: SGYSGK (Vir-4), SWPDGK (Vir-5), EECSCYPK (Vir-6) and VELIRGRK (Vir-7). Animals were monitored for 14 days after challenge with mouse-adapted virulent influenza virus strain A/California/7/09 mouse-adapted (H1N1pdm09) (A) and A/Philippines/2/82 X-79 (H3N2) (B) (904KB) Figure 3. Analysis of serum IgG antibody levels of BALB/c mice after triple immunization (868KB) |
14. | Coverage | Geo-spatial location, chronological period, research sample (gender, age, etc.) | |
15. | Rights | Copyright and permissions |
Copyright (c) 2024 Kotomina T.S., Sychev I.A., Rak A.Y., Wong P., Bazhina A.V., Isakova-Sivak I.N., Rudenko L.G.![]() This work is licensed under a Creative Commons Attribution 4.0 International License. |