Epidemic influenza virus nucleoprotein gene incorporated into vaccine influenza virus strain genome to optimize systemic and local T-cell immune response against live attenuated influenza vaccine
- Authors: Prokopenko P.I.1, Stepanova E.A.1, Matyushenko V.A.1, Chistyakova A.K.1, Kostromitina A.D.1, Kotomina T.S.1, Rak A.Y.1, Rubinstein A.A.1, Kudryavtsev I.V.1, Novitskaya V.V.1, Rudenko L.G.1, Isakova-Sivak I.N.1
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Affiliations:
- Institute of Experimental Medicine
- Issue: Vol 14, No 2 (2024)
- Pages: 371-380
- Section: ORIGINAL ARTICLES
- URL: https://journals.rcsi.science/2220-7619/article/view/262378
- DOI: https://doi.org/10.15789/2220-7619-EIV-17590
- ID: 262378
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Abstract
Introduction. Optimization of the vaccine-induced T-cell repertoire is one of the strategies to expand the spectrum of protective potential for live attenuated influenza vaccine (LAIV). LAIV cross-protective properties can be improved by introducing the nucleoprotein (NP) gene derived from epidemic parental virus into vaccine strain genome, i.e. by replacing the classical 6:2 genome formula with 5:3. The main objective of the present study was to detail evaluation for virus-specific systemic and tissue-resident memory T-cells subsets in mice immunized with seasonal H1N1 LAIV of the genome formula 6:2 and 5:3. Materials and methods. Two H1N1 LAIV strains with varying NP genes (LAIV 6:2 and LAIV 5:3) were generated using reverse genetics techniques. C57BL/6J mice were immunized intranasally with the vaccine candidates, twice, 3 weeks apart. Cells from the spleen and lung tissues were isolated 7 days after booster immunization to be stimulated with whole H1N1 influenza virus for assessing cytokine-producing memory CD44+CD62L– T-cells as well as expression of CD69 and CD103 surface markers using flow cytometry. Humoral murine serum immunity against H1N1 virus was assessed by ELISA. Results. The LAIV 5:3 vs classical 6:2 vaccine strain carrying the epidemic parental NP gene induced significantly more pronounced humoral immune response against recent influenza virus. The group of mice immunized with LAIV 5:3 demonstrated higher levels of virus-specific CD4+ and CD8+ effector memory T cells (TEM) in the spleen, including a subset of polyfunctional (IFNγ+TNFα+IL-2+) CD4+ TEM, compared to LAIV 6:2 group. Virus-specific memory T cell levels in lung tissues after immunization with LAIV 5:3 vs LAIV 6:2 also tended to increase, but no significant difference in stimulated tissue-resident CD69+CD103– and CD69+CD103+ T cells between the groups were found. Conclusion. Modification of the seasonal LAIV strain genome for updating its epitope composition allowed to enhance the virus-specific T-cell immune response both at systemic level and in lung tissues, thereby shoeing that the effectiveness of the vaccine against circulating influenza viruses can be potentially increased.
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##article.viewOnOriginalSite##About the authors
P. I. Prokopenko
Institute of Experimental Medicine
Author for correspondence.
Email: pi.prokopenko@gmail.com
Junior Researcher, A.A. Smorodintsev Department of Virology
Russian Federation, St. PetersburgE. A. Stepanova
Institute of Experimental Medicine
Email: pi.prokopenko@gmail.com
PhD (Biology), Leading Researcher, A.A. Smorodintsev Department of Virology
Russian Federation, St. PetersburgV. A. Matyushenko
Institute of Experimental Medicine
Email: pi.prokopenko@gmail.com
Researcher, A.A. Smorodintsev Department of Virology
Russian Federation, St. PetersburgA. K. Chistyakova
Institute of Experimental Medicine
Email: pi.prokopenko@gmail.com
Research Laboratory Assistant, A.A. Smorodintsev Department of Virology
Russian Federation, St. PetersburgA. D. Kostromitina
Institute of Experimental Medicine
Email: pi.prokopenko@gmail.com
Research Laboratory Assistant, A.A. Smorodintsev Department of Virology
Russian Federation, St. PetersburgT. S. Kotomina
Institute of Experimental Medicine
Email: pi.prokopenko@gmail.com
Researcher, A.A. Smorodintsev Department of Virology
Russian Federation, St. PetersburgA. Ya. Rak
Institute of Experimental Medicine
Email: pi.prokopenko@gmail.com
PhD (Biology), Senior Researcher, A.A. Smorodintsev Department of Virology
Russian Federation, St. PetersburgA. A. Rubinstein
Institute of Experimental Medicine
Email: pi.prokopenko@gmail.com
Junior Researcher, Cell Immunology Laboratory, Department of Immunology
Russian Federation, St. PetersburgI. V. Kudryavtsev
Institute of Experimental Medicine
Email: pi.prokopenko@gmail.com
PhD (Biology), Head of the Cell Immunology Laboratory, Department of Immunology
Russian Federation, St. PetersburgV. V. Novitskaya
Institute of Experimental Medicine
Email: pi.prokopenko@gmail.com
Research Laboratory Assistant, A.A. Smorodintsev Department of Virology
Russian Federation, St. PetersburgL. G. Rudenko
Institute of Experimental Medicine
Email: pi.prokopenko@gmail.com
DSc (Medicine), Professor, Head of A.A. Smorodintsev Department of Virology
Russian Federation, St. PetersburgI. N. Isakova-Sivak
Institute of Experimental Medicine
Email: pi.prokopenko@gmail.com
RAS Corresponding Member, DSc (Biology), Head of the Laboratory of Immunology and Prevention of Viral Infections, A.A. Smorodintsev Department of Virology
Russian Federation, St. PetersburgReferences
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