Email this article Features of immune response against influenza infection in animals vaccinated with recombinant cross-protective vaccine
- Authors: Tsybalova L.M.1, Stepanova L.A.1, Korotkov A.V.1, Shuklina M.A.1, Zaitseva M.V.1, Grishchenko V.I.1, Kotlyarov R.Y.2
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Affiliations:
- Smorodintsev Research Institute of Influenza, Ministry of Health of the Russian Federation
- Research Institute of Bioengineering, FIC «Fundamentals of Biotechnology» RAS
- Issue: Vol 9, No 3-4 (2019)
- Pages: 485-494
- Section: ORIGINAL ARTICLES
- Submitted: 08.11.2018
- Accepted: 30.05.2019
- Published: 14.11.2019
- URL: https://iimmun.ru/iimm/article/view/796
- DOI: https://doi.org/10.15789/2220-7619-2019-3-4-485-494
- ID: 796
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Abstract
Generating cross-reactive vaccines aimed at targeting all human influenza A virus subtypes is among high priority tasks in contemporary vaccinology. Such vaccines will be primarily demanded during pre-pandemic period as well as used to prime some population cohorts prior to vaccination with standard vaccines containing area-relevant epidemic virus. Unlike routine approach universal vaccines do not induce a sterilizing immunity, but significantly ameliorate overt infection and probable complications. Our study was aimed at evaluating characteristics of immune response in experimental animals primed with a candidate universal vaccine challenged with sublethal influenza A virus infection. Mice were immunized intranasally with the recombinant protein FlgH2-2-4M2e containing conservative peptides derived from two influenza A virus proteins: M2 protein ectodomain and 76–130 amino acid sequence from the second hemagglutinin (HA2) subunit genetically linked to bacterial flagellin protein, which is a ligand for Toll-like receptor 5 (TLR5). Control mice received saline. Two weeks after immunization, mice from both groups were infected with a sublethal dose of A/Aichi/2/68 AN3N2 influenza virus strain. Level of immunoglobulins G and A in the blood sera and bronchoalveolar lavages (BAL) were determined two weeks after immunization and 1 month post infection. Percentage of lung CD4+ T and CD4+ Tem (CD44+CD62L–) cells secreting cytokines TNFα, IFNγ, IL-2 was determined. Immunized vs. control mice responded to sublethal infection with the influenza virus by insignificant weight loss and more pronounced production of vaccine peptide-specific (M2e and aa76–130 HA2) and pan-influenza A/Aichi/2/68 virus IgG and A in the blood sera and BAL. After challenge the number of CD4+ T cells secreting cytokines TNFα and/or IL-2 in immunized mice significantly exceeded counterpart T cells in unimmunized animals that was true for both CD4+T and CD4+ Tem cells. Memory CD4+ T cells were previously shown to play a key role in the prime-boost event and heterosubtypic immune response. Thus, we were able to demonstrate a priming effect for recombinant cross-protective vaccine used in our experiment.
About the authors
L. M. Tsybalova
Smorodintsev Research Institute of Influenza, Ministry of Health of the Russian Federation
Author for correspondence.
Email: sovet@influenza.spb.ru
PhD, MD (Medicine), Head of the Department of Vaccinology, Head of the Laboratory of Influenza Vaccines, Advisor to the Director,
197376, St. Petersburg, Professora Popova str., 15/17
РоссияL. A. Stepanova
Smorodintsev Research Institute of Influenza, Ministry of Health of the Russian Federation
Email: fake@neicon.ru
PhD (Biology), Leading Researcher, Laboratory of Influenza Vaccines,
St. Petersburg
РоссияA. V. Korotkov
Smorodintsev Research Institute of Influenza, Ministry of Health of the Russian Federation
Email: fake@neicon.ru
Researcher, Laboratory of Influenza Vaccines,
St. Petersburg
M. A. Shuklina
Smorodintsev Research Institute of Influenza, Ministry of Health of the Russian Federation
Email: fake@neicon.ru
Junior Researcher, Laboratory for Influenza Vaccines,
St. Petersburg
РоссияM. V. Zaitseva
Smorodintsev Research Institute of Influenza, Ministry of Health of the Russian Federation
Email: fake@neicon.ru
Junior Researcher, Laboratory of Influenza Vaccines,
St. Petersburg
РоссияV. I. Grishchenko
Smorodintsev Research Institute of Influenza, Ministry of Health of the Russian Federation
Email: fake@neicon.ru
Junior Researcher, Laboratory of Influenza Vaccines,
St. Petersburg
РоссияR. Yu. Kotlyarov
Research Institute of Bioengineering, FIC «Fundamentals of Biotechnology» RAS
Email: fake@neicon.ru
PhD (Biology), Researcher, Department of Molecular Biology of Microorganisms,
Moscow
РоссияReferences
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СМИ зарегистрировано Федеральной службой по надзору в сфере связи, информационных технологий и массовых коммуникаций (Роскомнадзор).