Examining immune arms in mice immunized with site-specific influenza virus mutants
| Autor: | S. G. Markushin, N. K. Akhmatova, V. N. Stolpnikova, I. Iv. Akopova, A. A. Rtishchev, E. O. Kalinichenko |
|---|---|
| Jazyk: | ruština |
| Rok vydání: | 2020 |
| Předmět: |
0301 basic medicine
Immunology chemical and pharmacologic phenomena Infectious and parasitic diseases RC109-216 immunogenicity Major histocompatibility complex Virus influenza virus 03 medical and health sciences 0302 clinical medicine Immune system Antigen Reassortant Viruses Immunology and Allergy Cytotoxic T cell 030212 general & internal medicine IL-2 receptor subpopulations of leukocytes attenuation biology site-specific mutants phagocytosis Acquired immune system Virology 030104 developmental biology Infectious Diseases toll-like receptors biology.protein |
| Zdroj: | Infekciâ i Immunitet, Vol 10, Iss 2, Pp 295-304 (2020) |
| ISSN: | 2313-7398 2220-7619 |
| Popis: | 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. |
| Databáze: | OpenAIRE |
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