Features of immune response against influenza infection in animals vaccinated with recombinant cross-protective vaccine

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...

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Autores principales:	L. M. Tsybalova, L. A. Stepanova, A. V. Korotkov, M. A. Shuklina, M. V. Zaitseva, V. I. Grishchenko, R. Yu. Kotlyarov
Formato:	article
Lenguaje:	RU
Publicado:	Sankt-Peterburg : NIIÈM imeni Pastera 2019
Materias:	influenza a recombinant vaccine experimental animals immune response Infectious and parasitic diseases RC109-216
Acceso en línea:	https://doaj.org/article/772c70c0aa8746b58a1050dd91f199af
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spelling	oai:doaj.org-article:772c70c0aa8746b58a1050dd91f199af2021-11-22T07:09:53ZFeatures of immune response against influenza infection in animals vaccinated with recombinant cross-protective vaccine2220-76192313-739810.15789/2220-7619-2019-3-4-485-494https://doaj.org/article/772c70c0aa8746b58a1050dd91f199af2019-11-01T00:00:00Zhttps://www.iimmun.ru/iimm/article/view/796https://doaj.org/toc/2220-7619https://doaj.org/toc/2313-7398Generating 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.L. M. TsybalovaL. A. StepanovaA. V. KorotkovM. A. ShuklinaM. V. ZaitsevaV. I. GrishchenkoR. Yu. KotlyarovSankt-Peterburg : NIIÈM imeni Pasteraarticleinfluenza arecombinant vaccineexperimental animalsimmune responseInfectious and parasitic diseasesRC109-216RUInfekciâ i Immunitet, Vol 9, Iss 3-4, Pp 485-494 (2019)
institution	DOAJ
collection	DOAJ
language	RU
topic	influenza a recombinant vaccine experimental animals immune response Infectious and parasitic diseases RC109-216
spellingShingle	influenza a recombinant vaccine experimental animals immune response Infectious and parasitic diseases RC109-216 L. M. Tsybalova L. A. Stepanova A. V. Korotkov M. A. Shuklina M. V. Zaitseva V. I. Grishchenko R. Yu. Kotlyarov Features of immune response against influenza infection in animals vaccinated with recombinant cross-protective vaccine
description	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.
format	article
author	L. M. Tsybalova L. A. Stepanova A. V. Korotkov M. A. Shuklina M. V. Zaitseva V. I. Grishchenko R. Yu. Kotlyarov
author_facet	L. M. Tsybalova L. A. Stepanova A. V. Korotkov M. A. Shuklina M. V. Zaitseva V. I. Grishchenko R. Yu. Kotlyarov
author_sort	L. M. Tsybalova
title	Features of immune response against influenza infection in animals vaccinated with recombinant cross-protective vaccine
title_short	Features of immune response against influenza infection in animals vaccinated with recombinant cross-protective vaccine
title_full	Features of immune response against influenza infection in animals vaccinated with recombinant cross-protective vaccine
title_fullStr	Features of immune response against influenza infection in animals vaccinated with recombinant cross-protective vaccine
title_full_unstemmed	Features of immune response against influenza infection in animals vaccinated with recombinant cross-protective vaccine
title_sort	features of immune response against influenza infection in animals vaccinated with recombinant cross-protective vaccine
publisher	Sankt-Peterburg : NIIÈM imeni Pastera
publishDate	2019
url	https://doaj.org/article/772c70c0aa8746b58a1050dd91f199af
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Features of immune response against influenza infection in animals vaccinated with recombinant cross-protective vaccine

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