Intranasal immunization with a recombinant protein based on the M2e peptide and second subunit of influenza A viral hemagglutinin fragment induces a cross-protective humoral and Tcell response in mice

Development of vaccines with a broad-spectrum of protection is one of the priorities in the programs of influenza prevention. Recently, the conserved fragments of influenza virus proteins (M1, M2, NP, the second subunit of the hemagglutinin HA2) provoke interest of investigators as the object of the...

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Autores principales:	M. A Shuklina, L. A Stepanova, A. A. Kovaleva, A. V. Korotkov, A. A. Shaldzhyan, M. V. Zaitceva, E. I. Eletskaya, L. M. Tsybalova
Formato:	article
Lenguaje:	RU
Publicado:	SPb RAACI 2020
Materias:	influenza virus recombinant vaccine m2e ectodomain ha2 immune response hemagglutinin Immunologic diseases. Allergy RC581-607
Acceso en línea:	https://doaj.org/article/72a915dfe7c44f1985c6c7399e24de7e
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spelling	oai:doaj.org-article:72a915dfe7c44f1985c6c7399e24de7e2021-11-18T08:03:49ZIntranasal immunization with a recombinant protein based on the M2e peptide and second subunit of influenza A viral hemagglutinin fragment induces a cross-protective humoral and Tcell response in mice1563-06252313-741X10.15789/1563-0625-IIW-1584https://doaj.org/article/72a915dfe7c44f1985c6c7399e24de7e2020-04-01T00:00:00Zhttps://www.mimmun.ru/mimmun/article/view/1584https://doaj.org/toc/1563-0625https://doaj.org/toc/2313-741XDevelopment of vaccines with a broad-spectrum of protection is one of the priorities in the programs of influenza prevention. Recently, the conserved fragments of influenza virus proteins (M1, M2, NP, the second subunit of the hemagglutinin HA2) provoke interest of investigators as the object of the development a broad-spectrum vaccines. Low immunogenicity present a problem when developing vaccines based on such conserved fragments. However, fusion of low immunogenic antigens into the high immunogenic carrier protein may significantly enhance their immunogenicity. The candidate vaccine protein Flg-HA2-2-4M2e was developed which containins two highly conserved viral antigens (the ectodomain of the M2 protein (M2e), 76130 region of the second subunit of HA2), fused with flagellin as a carrier protein. Flagellin (bacterial flagella protein) is a natural ligand of TLR-5, and has a strong adjuvant activity at different ways of its administration. The purpose of this study was to assess development of humoral and T cell immune response, along with broad-spectrum protection after mice immunization with the candidate Flg-HA2-2-4M2e vaccine protein. Mice were immunized intranasally three times with two-week intervals. Two weeks after the final immunization, the mice were challenged at the 5 LD50 dose with influenza viruses A/California/07/09 (H1N1) pdm09 (phylogenetic group I), or A/Shanghai/2/2013 (H7N9) (phylogenetic group II). The results obtained in this study showed induction of strong M2e-specific humoral response (serum IgG and A) in the immunized mice. Immunization with recombinant protein stimulated formation of M2e-specific and virus-specific CD4+ and CD8+T cells in lung which produced TNFα or IFNγ. Production of antigen-specific effector and central memory T cells was also detected in lungs of immunized mice. The formation of cross-protective immunity in immunized mice was demonstrated in a model of lethal influenza infection. The experimental animals were almost completely protected from the high dose of the pandemic virus A/H1N1pdm09, and highly pathogenic avian influenza A/H7N9 (90-100% survival). We also evaluated the changes of antigen-specific immune response in immunized mice after sublethal infection with A/H3N2 influenza virus. Mice of control and experimental groups were infected with MID100 of influenza virus A/Aichi/2/68 (H3N2). It was shown that the M2e-specific response (IgG, IgA) was significantly increased in immunized mice after sublethal infection with influenza virus A/H3N2, and we detected the changes in profile of M2e-specific IgG subclasses. Following sublethal infection in immunized mice, the proportion of M2e-specific IgG2a was increased 10-fold. The results showed that the recombinant protein Flg-HA2-2-4M2e is a promising candidate for development of universal vaccines, which induces a protective humoral and T-cell response to conserved viral epitopes and protects against influenza A viruses of both phylogenetic groups.M. A ShuklinaL. A StepanovaA. A. KovalevaA. V. KorotkovA. A. ShaldzhyanM. V. ZaitcevaE. I. EletskayaL. M. TsybalovaSPb RAACIarticleinfluenza virusrecombinant vaccinem2e ectodomainha2immune responsehemagglutininImmunologic diseases. AllergyRC581-607RUMedicinskaâ Immunologiâ, Vol 22, Iss 2, Pp 357-370 (2020)
institution	DOAJ
collection	DOAJ
language	RU
topic	influenza virus recombinant vaccine m2e ectodomain ha2 immune response hemagglutinin Immunologic diseases. Allergy RC581-607
spellingShingle	influenza virus recombinant vaccine m2e ectodomain ha2 immune response hemagglutinin Immunologic diseases. Allergy RC581-607 M. A Shuklina L. A Stepanova A. A. Kovaleva A. V. Korotkov A. A. Shaldzhyan M. V. Zaitceva E. I. Eletskaya L. M. Tsybalova Intranasal immunization with a recombinant protein based on the M2e peptide and second subunit of influenza A viral hemagglutinin fragment induces a cross-protective humoral and Tcell response in mice
description	Development of vaccines with a broad-spectrum of protection is one of the priorities in the programs of influenza prevention. Recently, the conserved fragments of influenza virus proteins (M1, M2, NP, the second subunit of the hemagglutinin HA2) provoke interest of investigators as the object of the development a broad-spectrum vaccines. Low immunogenicity present a problem when developing vaccines based on such conserved fragments. However, fusion of low immunogenic antigens into the high immunogenic carrier protein may significantly enhance their immunogenicity. The candidate vaccine protein Flg-HA2-2-4M2e was developed which containins two highly conserved viral antigens (the ectodomain of the M2 protein (M2e), 76130 region of the second subunit of HA2), fused with flagellin as a carrier protein. Flagellin (bacterial flagella protein) is a natural ligand of TLR-5, and has a strong adjuvant activity at different ways of its administration. The purpose of this study was to assess development of humoral and T cell immune response, along with broad-spectrum protection after mice immunization with the candidate Flg-HA2-2-4M2e vaccine protein. Mice were immunized intranasally three times with two-week intervals. Two weeks after the final immunization, the mice were challenged at the 5 LD50 dose with influenza viruses A/California/07/09 (H1N1) pdm09 (phylogenetic group I), or A/Shanghai/2/2013 (H7N9) (phylogenetic group II). The results obtained in this study showed induction of strong M2e-specific humoral response (serum IgG and A) in the immunized mice. Immunization with recombinant protein stimulated formation of M2e-specific and virus-specific CD4+ and CD8+T cells in lung which produced TNFα or IFNγ. Production of antigen-specific effector and central memory T cells was also detected in lungs of immunized mice. The formation of cross-protective immunity in immunized mice was demonstrated in a model of lethal influenza infection. The experimental animals were almost completely protected from the high dose of the pandemic virus A/H1N1pdm09, and highly pathogenic avian influenza A/H7N9 (90-100% survival). We also evaluated the changes of antigen-specific immune response in immunized mice after sublethal infection with A/H3N2 influenza virus. Mice of control and experimental groups were infected with MID100 of influenza virus A/Aichi/2/68 (H3N2). It was shown that the M2e-specific response (IgG, IgA) was significantly increased in immunized mice after sublethal infection with influenza virus A/H3N2, and we detected the changes in profile of M2e-specific IgG subclasses. Following sublethal infection in immunized mice, the proportion of M2e-specific IgG2a was increased 10-fold. The results showed that the recombinant protein Flg-HA2-2-4M2e is a promising candidate for development of universal vaccines, which induces a protective humoral and T-cell response to conserved viral epitopes and protects against influenza A viruses of both phylogenetic groups.
format	article
author	M. A Shuklina L. A Stepanova A. A. Kovaleva A. V. Korotkov A. A. Shaldzhyan M. V. Zaitceva E. I. Eletskaya L. M. Tsybalova
author_facet	M. A Shuklina L. A Stepanova A. A. Kovaleva A. V. Korotkov A. A. Shaldzhyan M. V. Zaitceva E. I. Eletskaya L. M. Tsybalova
author_sort	M. A Shuklina
title	Intranasal immunization with a recombinant protein based on the M2e peptide and second subunit of influenza A viral hemagglutinin fragment induces a cross-protective humoral and Tcell response in mice
title_short	Intranasal immunization with a recombinant protein based on the M2e peptide and second subunit of influenza A viral hemagglutinin fragment induces a cross-protective humoral and Tcell response in mice
title_full	Intranasal immunization with a recombinant protein based on the M2e peptide and second subunit of influenza A viral hemagglutinin fragment induces a cross-protective humoral and Tcell response in mice
title_fullStr	Intranasal immunization with a recombinant protein based on the M2e peptide and second subunit of influenza A viral hemagglutinin fragment induces a cross-protective humoral and Tcell response in mice
title_full_unstemmed	Intranasal immunization with a recombinant protein based on the M2e peptide and second subunit of influenza A viral hemagglutinin fragment induces a cross-protective humoral and Tcell response in mice
title_sort	intranasal immunization with a recombinant protein based on the m2e peptide and second subunit of influenza a viral hemagglutinin fragment induces a cross-protective humoral and tcell response in mice
publisher	SPb RAACI
publishDate	2020
url	https://doaj.org/article/72a915dfe7c44f1985c6c7399e24de7e
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Intranasal immunization with a recombinant protein based on the M2e peptide and second subunit of influenza A viral hemagglutinin fragment induces a cross-protective humoral and Tcell response in mice

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