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  1. Article: SARS-CoV-2 Vaccines: Inactivation by Gamma Irradiation for T and B Cell Immunity.

    Mullbacher, Arno / Pardo, Julian / Furuya, Yoichi

    Pathogens (Basel, Switzerland)

    2020  Volume 9, Issue 11

    Abstract: Despite accumulating preclinical data demonstrating a crucial role of cytotoxic T cell immunity during viral infections, ongoing efforts on developing COVID-19 vaccines are mostly focused on antibodies. In this commentary article, we discuss potential ... ...

    Abstract Despite accumulating preclinical data demonstrating a crucial role of cytotoxic T cell immunity during viral infections, ongoing efforts on developing COVID-19 vaccines are mostly focused on antibodies. In this commentary article, we discuss potential benefits of cytotoxic T cells in providing long-term protection against COVID-19. Further, we propose that gamma-ray irradiation, which is a previously tested inactivation method, may be utilized to prepare an experimental COVID-19 vaccine that can provide balanced immunity involving both B and T cells.
    Keywords covid19
    Language English
    Publishing date 2020-11-10
    Publishing country Switzerland
    Document type Journal Article
    ZDB-ID 2695572-6
    ISSN 2076-0817
    ISSN 2076-0817
    DOI 10.3390/pathogens9110928
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  2. Article ; Online: Type I IFN exhaustion is a host defence protecting against secondary bacterial infections.

    Furuya, Y / Müllbacher, A

    Scandinavian journal of immunology

    2013  Volume 78, Issue 5, Page(s) 395–400

    Abstract: Type I interferons (IFN-I) have been known for decades for their indispensable role in curtailing viral infections. It is, however, now also increasingly recognized that IFN-I is detrimental to the host in combating a number of bacterial infections. We ... ...

    Abstract Type I interferons (IFN-I) have been known for decades for their indispensable role in curtailing viral infections. It is, however, now also increasingly recognized that IFN-I is detrimental to the host in combating a number of bacterial infections. We have previously reported that viral infections induce partial lymphocyte activation, characterized by significant increases in the cell surface expression of CD69 and CD86, but not CD25. This systemic partial activation of lymphocytes, mediated by IFN-I, is rapid and is followed by a period of IFN-I unresponsiveness. Here we propose that IFN-I exhaustion that occurs soon after a primary viral infection may be a host response protecting it from secondary bacterial infections.
    MeSH term(s) Animals ; Bacterial Infections/immunology ; Coinfection/immunology ; Interferon Type I/immunology ; Lymphocyte Activation/immunology ; Lymphocytes/immunology ; Mice ; Virus Diseases/immunology
    Chemical Substances Interferon Type I
    Keywords covid19
    Language English
    Publishing date 2013-09-04
    Publishing country England
    Document type Journal Article ; Review
    ZDB-ID 120476-2
    ISSN 1365-3083 ; 0300-9475
    ISSN (online) 1365-3083
    ISSN 0300-9475
    DOI 10.1111/sji.12107
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  3. Article: SARS-CoV-2 Vaccines: Inactivation by Gamma Irradiation for T and B Cell Immunity

    Mullbacher, Arno / Pardo, Julian / Furuya, Yoichi

    Pathogens. 2020 Nov. 10, v. 9, no. 11

    2020  

    Abstract: Despite accumulating preclinical data demonstrating a crucial role of cytotoxic T cell immunity during viral infections, ongoing efforts on developing COVID-19 vaccines are mostly focused on antibodies. In this commentary article, we discuss potential ... ...

    Abstract Despite accumulating preclinical data demonstrating a crucial role of cytotoxic T cell immunity during viral infections, ongoing efforts on developing COVID-19 vaccines are mostly focused on antibodies. In this commentary article, we discuss potential benefits of cytotoxic T cells in providing long-term protection against COVID-19. Further, we propose that gamma-ray irradiation, which is a previously tested inactivation method, may be utilized to prepare an experimental COVID-19 vaccine that can provide balanced immunity involving both B and T cells.
    Keywords B-lymphocytes ; Coronavirus infections ; T-lymphocytes ; antibodies ; cytotoxicity ; gamma radiation ; immunity ; inactivation ; irradiation ; pathogens ; vaccines
    Language English
    Dates of publication 2020-1110
    Publishing place Multidisciplinary Digital Publishing Institute
    Document type Article
    Note NAL-light
    ZDB-ID 2695572-6
    ISSN 2076-0817
    ISSN 2076-0817
    DOI 10.3390/pathogens9110928
    Database NAL-Catalogue (AGRICOLA)

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  4. Article: Cell-mediated cytotoxicity in recovery from poxvirus infections.

    Müllbacher, Arno

    Reviews in medical virology

    2003  Volume 13, Issue 4, Page(s) 223–232

    Abstract: The availability of mutant and gene targeted knockout mice with defects in components of cellular cytotoxicity mediated by either the Fas or the exocytosis pathway permitted an analysis of their role in recovery from poxvirus infections. Ectromelia (EV), ...

    Abstract The availability of mutant and gene targeted knockout mice with defects in components of cellular cytotoxicity mediated by either the Fas or the exocytosis pathway permitted an analysis of their role in recovery from poxvirus infections. Ectromelia (EV), a natural mouse pathogen causing mousepox, the closely related orthopoxviruses cow pox (CPV) and vaccinia virus (VV), each encode serpins that inhibit Fas mediated apoptosis and lysis of target cells. Nevertheless, distinct differences were seen when the three viruses were inoculated into perforin-deficient mice: highly resistant C57Bl/6 mice became susceptible to low doses of EV; resistance to CPV increased whereas there was no effect on VV infections. Absence of the cytolytic granule associated granzymes (gzm) A and B rendered C57Bl/6 mice increasingly more susceptible to EV infections. Lack of both gzms rendered them as susceptible as perforin deficient mice, despite the presence of functionally active perforin. Elevated EV titres in liver and spleen of gzmA x B deficient mice, early after infection and before cytotoxic T cells were detectable, strongly suggests that these two gzms exert an antiviral effect by a mechanism distinct from effector molecules of NK and cytotoxic T cells.
    MeSH term(s) Animals ; Cowpox virus/immunology ; Cowpox virus/pathogenicity ; Cytotoxicity, Immunologic ; Disease Models, Animal ; Ectromelia virus/immunology ; Ectromelia virus/pathogenicity ; Exocytosis/immunology ; Granzymes ; Membrane Glycoproteins/deficiency ; Membrane Glycoproteins/genetics ; Membrane Glycoproteins/immunology ; Mice ; Mice, Inbred C57BL ; Mice, Knockout ; Models, Immunological ; Perforin ; Pore Forming Cytotoxic Proteins ; Poxviridae Infections/enzymology ; Poxviridae Infections/immunology ; Poxviridae Infections/virology ; Serine Endopeptidases/deficiency ; Serine Endopeptidases/genetics ; Serine Endopeptidases/immunology ; T-Lymphocytes, Cytotoxic/immunology ; Vaccinia virus/immunology ; Vaccinia virus/pathogenicity ; fas Receptor/immunology
    Chemical Substances Membrane Glycoproteins ; Pore Forming Cytotoxic Proteins ; fas Receptor ; Perforin (126465-35-8) ; Granzymes (EC 3.4.21.-) ; Gzmb protein, mouse (EC 3.4.21.-) ; Serine Endopeptidases (EC 3.4.21.-)
    Language English
    Publishing date 2003-07
    Publishing country England
    Document type Journal Article ; Review
    ZDB-ID 1086043-5
    ISSN 1099-1654 ; 1052-9276
    ISSN (online) 1099-1654
    ISSN 1052-9276
    DOI 10.1002/rmv.381
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  5. Article: Mysteries of type I IFN response: benefits versus detriments.

    Furuya, Yoichi / Ludewick, Herbert P / Müllbacher, Arno

    Frontiers in immunology

    2015  Volume 6, Page(s) 21

    Language English
    Publishing date 2015
    Publishing country Switzerland
    Document type Journal Article
    ZDB-ID 2606827-8
    ISSN 1664-3224
    ISSN 1664-3224
    DOI 10.3389/fimmu.2015.00021
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  6. Article: Murine cytotoxic T-cell response to alphavirus is associated mainly withH- 2D ( k ).

    Müllbacher, A / Blanden, R V

    Immunogenetics

    2011  Volume 7, Issue 1, Page(s) 551–561

    Abstract: A secondary in vitro response to alphaviruses Bebaru, Sindbis, and Semliki Forest is described. Optimum response appears at day 5-6 of culture. The cells responsible for lytic activity are nonadherent, Φ-positive, Ig(-), and mainly Ly-2.1 positive. Out ... ...

    Abstract A secondary in vitro response to alphaviruses Bebaru, Sindbis, and Semliki Forest is described. Optimum response appears at day 5-6 of culture. The cells responsible for lytic activity are nonadherent, Φ-positive, Ig(-), and mainly Ly-2.1 positive. Out of five haplotypes tested (H- 2 ( d ),H- 2 ( b ),H- 2 ( s ),H- 2 ( q ), andH- 2 ( k )) onlyH- 2 ( k ) was a responder. Genetic mapping of the response located it solely in theD region of theH- 2 complex. The other four haplotypes responded with a high antiself activity after a second stimulation with viruses. This antiself response also maps in theD region of theH- 2 complex. No complementation was observed in F(1) hybrids between responder and nonresponder strains.
    Language English
    Publishing date 2011-02-08
    Publishing country United States
    Document type Journal Article
    ZDB-ID 186560-2
    ISSN 1432-1211 ; 0093-7711
    ISSN (online) 1432-1211
    ISSN 0093-7711
    DOI 10.1007/BF01844044
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  7. Article: Hypothesis: MHC class I, rather than just a flagpole for CD8+ T cells is also a protease in its own right.

    Müllbacher, A

    Immunology and cell biology

    1997  Volume 75, Issue 3, Page(s) 310–317

    Abstract: Ever since the discovery of MHC class I restriction and the onslaught of the dual receptor hypothesis, MHC class I has been perceived as a passive entity in TCR recognition and the appropriate antigen processing and presentation pathways. However, ... ...

    Abstract Ever since the discovery of MHC class I restriction and the onslaught of the dual receptor hypothesis, MHC class I has been perceived as a passive entity in TCR recognition and the appropriate antigen processing and presentation pathways. However, numerous experimental observations and theoretical considerations are difficult or unable to be explained by the accepted mechanism of class I antigen presentation. Proteases within and outside the endoplasmic reticulum (ER) are evoked to be solely responsible for the generation of the appropriate 8-10 amino acid-long peptides associated with MHC class I. A MHC class I with site-restricted ER protease activity would overcome most of the present difficulties in explaining MHC class I antigen presentation.
    MeSH term(s) Amino Acid Sequence ; Animals ; Antigen Presentation ; CD8-Positive T-Lymphocytes/enzymology ; CD8-Positive T-Lymphocytes/immunology ; Endopeptidases/metabolism ; Histocompatibility Antigens Class I/metabolism ; Humans ; Models, Biological ; Molecular Sequence Data ; Peptides/genetics ; Peptides/immunology ; Peptides/metabolism ; Protein Binding ; Viral Proteins/genetics ; Viral Proteins/immunology ; Viral Proteins/metabolism
    Chemical Substances Histocompatibility Antigens Class I ; Peptides ; Viral Proteins ; Endopeptidases (EC 3.4.-)
    Language English
    Publishing date 1997-06
    Publishing country United States
    Document type Journal Article ; Review
    ZDB-ID 284057-1
    ISSN 1440-1711 ; 0818-9641
    ISSN (online) 1440-1711
    ISSN 0818-9641
    DOI 10.1038/icb.1997.47
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  8. Article ; Online: Ectromelia virus N1L is essential for virulence but not dissemination in a classical model of mousepox.

    Melo-Silva, Carolina R / Tscharke, David C / Lobigs, Mario / Koskinen, Aulikki / Müllbacher, Arno / Regner, Matthias

    Virus research

    2017  Volume 228, Page(s) 61–65

    Abstract: Mousepox is caused by the orthopoxvirus ectromelia virus (ECTV), and is thought to be transmitted via skin abrasions. We studied the ECTV virulence factor N1 following subcutaneous infection of mousepox-susceptible BALB/c mice. In this model, ECTV ... ...

    Abstract Mousepox is caused by the orthopoxvirus ectromelia virus (ECTV), and is thought to be transmitted via skin abrasions. We studied the ECTV virulence factor N1 following subcutaneous infection of mousepox-susceptible BALB/c mice. In this model, ECTV lacking N1L gene was attenuated more than 1000-fold compared with wild-type virus and replication was profoundly reduced as early as four days after infection. However, in contrast to data from an intranasal model, N1 protein was not required for virus dissemination. Further, neither T cell nor cytokine responses were enhanced in the absence of N1. Together with the early timing of reduced virus titres, this suggests that in a cutaneous model, N1 exerts its function at the level of infected cells or in the inhibition of the very earliest effectors of innate immunity.
    Language English
    Publishing date 2017-01-15
    Publishing country Netherlands
    Document type Journal Article
    ZDB-ID 605780-9
    ISSN 1872-7492 ; 0168-1702
    ISSN (online) 1872-7492
    ISSN 0168-1702
    DOI 10.1016/j.virusres.2016.11.017
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  9. Article ; Online: The gamma-irradiated influenza vaccine and the prospect of producing safe vaccines in general.

    Alsharifi, Mohammed / Müllbacher, Arno

    Immunology and cell biology

    2009  Volume 88, Issue 2, Page(s) 103–104

    MeSH term(s) Drug-Related Side Effects and Adverse Reactions ; Gamma Rays ; Humans ; Immunity, Cellular/radiation effects ; Immunity, Humoral/radiation effects ; Influenza Vaccines/biosynthesis ; Influenza Vaccines/immunology ; Influenza Vaccines/radiation effects ; Orthomyxoviridae/immunology ; Orthomyxoviridae/radiation effects ; Vaccines, Inactivated/biosynthesis ; Vaccines, Inactivated/immunology ; Vaccines, Inactivated/radiation effects ; Virus Inactivation/radiation effects ; World Health Organization
    Chemical Substances Influenza Vaccines ; Vaccines, Inactivated
    Language English
    Publishing date 2009-10-27
    Publishing country United States
    Document type Letter
    ZDB-ID 284057-1
    ISSN 1440-1711 ; 0818-9641
    ISSN (online) 1440-1711
    ISSN 0818-9641
    DOI 10.1038/icb.2009.81
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  10. Article: The long-term maintenance of cytotoxic T cell memory does not require persistence of antigen.

    Müllbacher, A

    The Journal of experimental medicine

    1994  Volume 179, Issue 1, Page(s) 317–321

    Abstract: I have used the transfer of primed lymphocytes into syngeneic irradiated recipients to investigate whether the persistence of antigen is required in the long-term maintenance of cytolytic T cell memory to influenza virus. Animals were immunized with ... ...

    Abstract I have used the transfer of primed lymphocytes into syngeneic irradiated recipients to investigate whether the persistence of antigen is required in the long-term maintenance of cytolytic T cell memory to influenza virus. Animals were immunized with influenza virus (A/WSN) and used 17 wk later as either donors for T cells or as lethally irradiated recipients. Naive age-matched mice served as controls. At intervals of 4, 8, 16, and 25 wk after T cell transfer, experimental and control groups were immunized with a heterologous virus (A/JAP) and splenocytes tested for lytic activity to influenza virus 3 and 6 d after immunization. Lytic activity 3 d after infection (a property exclusive to a memory cytotoxic T cell response) (Effros, R. B., J. Bennink, and P. C. Doherty. 1978. Cell. Immunol. 36:345.; and Hill, A. B., R. V. Blanden, C. R. Parrish, and A. Müllbacher. 1992. Immunol. Cell Biol. 70:259), was only observed by primed and naive irradiated recipients reconstituted with memory T cells. No day 3 responses were observed when naive T cells were transferred into irradiated primed or unprimed recipients. These observations demonstrate that cytolytic T cell memory to influenza virus is long lived in the absence of antigen.
    MeSH term(s) Animals ; Antigens, Viral/analysis ; Antigens, Viral/immunology ; Female ; Immunologic Memory ; Influenza A virus/immunology ; Mice ; Mice, Inbred BALB C ; Mice, Inbred CBA ; T-Lymphocytes, Cytotoxic/immunology ; Tumor Cells, Cultured
    Chemical Substances Antigens, Viral
    Language English
    Publishing date 1994-01-01
    Publishing country United States
    Document type Journal Article
    ZDB-ID 218343-2
    ISSN 1540-9538 ; 0022-1007
    ISSN (online) 1540-9538
    ISSN 0022-1007
    DOI 10.1084/jem.179.1.317
    Database MEDical Literature Analysis and Retrieval System OnLINE

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