Examining immune arms in mice immunized with site-specific influenza virus mutants

Site-specific mutants as candidates for live influenza vaccines were resulted from directly introducing into the genome of the pathogenic influenza virus A/WSN/33 (H1N1) strain ts mutations derived from the genes encoding the polymerase complex proteins from some cold-adapted strains serving as atte...

Descripción completa

Guardado en:

Detalles Bibliográficos
Autores principales:	S. G. Markushin, N. K. Akhmatova, V. N. Stolpnikova, I. Iv. Akopova, A. A. Rtishchev, E. O. Kalinichenko
Formato:	article
Lenguaje:	RU
Publicado:	Sankt-Peterburg : NIIÈM imeni Pastera 2020
Materias:	influenza virus site-specific mutants attenuation immunogenicity subpopulations of leukocytes toll-like receptors phagocytosis Infectious and parasitic diseases RC109-216
Acceso en línea:	https://doaj.org/article/ad213b09b7d64c399cf27b0a73a32462
Etiquetas:	Agregar Etiqueta Sin Etiquetas, Sea el primero en etiquetar este registro!

id	oai:doaj.org-article:ad213b09b7d64c399cf27b0a73a32462
record_format	dspace
spelling	oai:doaj.org-article:ad213b09b7d64c399cf27b0a73a324622021-11-22T07:09:54ZExamining immune arms in mice immunized with site-specific influenza virus mutants2220-76192313-739810.15789/2220-7619-EIA-1175https://doaj.org/article/ad213b09b7d64c399cf27b0a73a324622020-05-01T00:00:00Zhttps://www.iimmun.ru/iimm/article/view/1175https://doaj.org/toc/2220-7619https://doaj.org/toc/2313-7398Site-specific mutants as candidates for live influenza vaccines were resulted from directly introducing into the genome of the pathogenic influenza virus A/WSN/33 (H1N1) strain ts mutations derived from the genes encoding the polymerase complex proteins from some cold-adapted strains serving as attenuation donor. Here we present the data of a comparative study examining immune system arms in mice immunized intranasally with influenza virus mutants and classical cold-adapted reassortant obtained by crossing cold-adapted strain Donor A/Krasnodar/101/35/59 (H2N2) with strain A/WSN/33 (H1N1) bearing surface antigens (hemagglutinin and neuraminidase) similar to mutants. Immunophenotyping mononuclear leukocytes from immunized mice indicated at moderate suppressive effect after using site-specific mutant and the HA reassortant viruses on some immune cell subsets. All viruses in immunized mice resulted in activation of certain lymphocyte subsets including MHC II-positive cells, CD45+/CD19+ B lymphocytes and natural killer cells (CD16/32+/CD3–). Timescale and magnitude of activation markedly differed for each cell subsets. Mice immunized with mutants M26 and U2 peaked with count of CD16/32+/CD3– expressing cells on day 2 after the second immunization compared with control (p < 0.05) that may suggest about an important role for NK cells in activating immune response. In contrast, no significant changes were observed during the study in percentage of CD4+/CD25+/Fox P3 regulatory T cells, CD4+ T helpers and CD8+ cytotoxic cells, except for a sharply decreased count of activated CD4+/CD25+ cells (4-fold) on day 7 after immunization with mutant virus M26. Moreover, mutants U2 and M26 more moderately increased percentage of TLR2- and TLR4-positive cells. The viruses studied ambiguously affected count of TLR9-expressing cells in immunized animals. All viruses increased phagocytic activity in monocytes, but not neutrophils. Despite the moderate activation of innate and adaptive immunity arms, site-specific mutants more profoundly affected humoral reactions inducing increased antibody titers, so that immunogenicity of mutant viruses was higher than that of the cold-adapted reassortant. Thus, the findings hold a promise of using site-specific mutants as live influenza vaccines.S. G. MarkushinN. K. AkhmatovaV. N. StolpnikovaI. Iv. AkopovaA. A. RtishchevE. O. KalinichenkoSankt-Peterburg : NIIÈM imeni Pasteraarticleinfluenza virussite-specific mutantsattenuationimmunogenicitysubpopulations of leukocytestoll-like receptorsphagocytosisInfectious and parasitic diseasesRC109-216RUInfekciâ i Immunitet, Vol 10, Iss 2, Pp 295-304 (2020)
institution	DOAJ
collection	DOAJ
language	RU
topic	influenza virus site-specific mutants attenuation immunogenicity subpopulations of leukocytes toll-like receptors phagocytosis Infectious and parasitic diseases RC109-216
spellingShingle	influenza virus site-specific mutants attenuation immunogenicity subpopulations of leukocytes toll-like receptors phagocytosis Infectious and parasitic diseases RC109-216 S. G. Markushin N. K. Akhmatova V. N. Stolpnikova I. Iv. Akopova A. A. Rtishchev E. O. Kalinichenko Examining immune arms in mice immunized with site-specific influenza virus mutants
description	Site-specific mutants as candidates for live influenza vaccines were resulted from directly introducing into the genome of the pathogenic influenza virus A/WSN/33 (H1N1) strain ts mutations derived from the genes encoding the polymerase complex proteins from some cold-adapted strains serving as attenuation donor. Here we present the data of a comparative study examining immune system arms in mice immunized intranasally with influenza virus mutants and classical cold-adapted reassortant obtained by crossing cold-adapted strain Donor A/Krasnodar/101/35/59 (H2N2) with strain A/WSN/33 (H1N1) bearing surface antigens (hemagglutinin and neuraminidase) similar to mutants. Immunophenotyping mononuclear leukocytes from immunized mice indicated at moderate suppressive effect after using site-specific mutant and the HA reassortant viruses on some immune cell subsets. All viruses in immunized mice resulted in activation of certain lymphocyte subsets including MHC II-positive cells, CD45+/CD19+ B lymphocytes and natural killer cells (CD16/32+/CD3–). Timescale and magnitude of activation markedly differed for each cell subsets. Mice immunized with mutants M26 and U2 peaked with count of CD16/32+/CD3– expressing cells on day 2 after the second immunization compared with control (p < 0.05) that may suggest about an important role for NK cells in activating immune response. In contrast, no significant changes were observed during the study in percentage of CD4+/CD25+/Fox P3 regulatory T cells, CD4+ T helpers and CD8+ cytotoxic cells, except for a sharply decreased count of activated CD4+/CD25+ cells (4-fold) on day 7 after immunization with mutant virus M26. Moreover, mutants U2 and M26 more moderately increased percentage of TLR2- and TLR4-positive cells. The viruses studied ambiguously affected count of TLR9-expressing cells in immunized animals. All viruses increased phagocytic activity in monocytes, but not neutrophils. Despite the moderate activation of innate and adaptive immunity arms, site-specific mutants more profoundly affected humoral reactions inducing increased antibody titers, so that immunogenicity of mutant viruses was higher than that of the cold-adapted reassortant. Thus, the findings hold a promise of using site-specific mutants as live influenza vaccines.
format	article
author	S. G. Markushin N. K. Akhmatova V. N. Stolpnikova I. Iv. Akopova A. A. Rtishchev E. O. Kalinichenko
author_facet	S. G. Markushin N. K. Akhmatova V. N. Stolpnikova I. Iv. Akopova A. A. Rtishchev E. O. Kalinichenko
author_sort	S. G. Markushin
title	Examining immune arms in mice immunized with site-specific influenza virus mutants
title_short	Examining immune arms in mice immunized with site-specific influenza virus mutants
title_full	Examining immune arms in mice immunized with site-specific influenza virus mutants
title_fullStr	Examining immune arms in mice immunized with site-specific influenza virus mutants
title_full_unstemmed	Examining immune arms in mice immunized with site-specific influenza virus mutants
title_sort	examining immune arms in mice immunized with site-specific influenza virus mutants
publisher	Sankt-Peterburg : NIIÈM imeni Pastera
publishDate	2020
url	https://doaj.org/article/ad213b09b7d64c399cf27b0a73a32462
work_keys_str_mv	AT sgmarkushin examiningimmunearmsinmiceimmunizedwithsitespecificinfluenzavirusmutants AT nkakhmatova examiningimmunearmsinmiceimmunizedwithsitespecificinfluenzavirusmutants AT vnstolpnikova examiningimmunearmsinmiceimmunizedwithsitespecificinfluenzavirusmutants AT iivakopova examiningimmunearmsinmiceimmunizedwithsitespecificinfluenzavirusmutants AT aartishchev examiningimmunearmsinmiceimmunizedwithsitespecificinfluenzavirusmutants AT eokalinichenko examiningimmunearmsinmiceimmunizedwithsitespecificinfluenzavirusmutants
_version_	1718417936974086144

Examining immune arms in mice immunized with site-specific influenza virus mutants

Ejemplares similares