121 research outputs found
Matthias Regner House
No full textView: Entry façade with full front porch and side façadeLocation: Fredericksburghttps://mavmatrix.uta.edu/jchenry_texasarch/4334/thumbnail.jp
Matthias Regner House
No full textView: Entry façade with full front porchLocation: Fredericksburghttps://mavmatrix.uta.edu/jchenry_texasarch/4333/thumbnail.jp
Intranasal flu vaccine protective against seasonal and H5N1 avian influenza infections
No full textBackground Influenza A (flu) virus causes significant morbidity and mortality worldwide, and current vaccines require annual updating to protect against the rapidly arising antigenic variations due to antigenic shift and drift. In fact, current subunit or split flu vaccines rely exclusively on antibody responses for protection and do not induce cytotoxic T (Tc) cell responses, which are broadly cross-reactive between virus strains. We have previously reported that γ-ray inactivated flu virus can induce cross-reactive Tc cell responses. Methodology/Principal Finding Here, we report that intranasal administration of purified γ-ray inactivated human influenza A virus preparations (γ-Flu) effectively induces heterotypic and cross-protective immunity. A single intranasal administration of γ-A/PR8[H1N1] protects mice against lethal H5N1 and other heterotypic infections. Conclusions/Significance Intranasal γ-Flu represents a unique approach for a cross-protective vaccine against both seasonal as well as possible future pandemic influenza A virus infections.Mohammed Alsharifi, Yoichi Furuya, Timothy R. Bowden, Mario Lobigs, Aulikki Koskinen, Matthias Regner, Lee Trinidad, David B. Boyle and Arno Müllbache
Cytoxic T cells are the predominant players providing cross-protective immunity induced by y-irradiated influenza A viruses
No full textWe previously demonstrated that a single dose of nonadjuvanted intranasal -irradiated influenza A virus can provide robust protection in mice against both homologous and heterosubtypic challenges, including challenge with an H5N1 avian virus strain. We investigated the mechanism behind the observed cross-protection to define which arms of the adaptive immune response are involved in mediating this protection. Studies with gene knockout mice showed the cross-protective immunity to be mediated mainly by T cells and to be dependent on the cytolytic effector molecule perforin. Adoptive transfer of memory T cells from immunized mice, but not of memory B cells, protected naïve recipients against lethal heterosubtypic influenza virus challenge. Furthermore, -irradiated influenza viruses induced cross-reactive Tc-cell responses but not cross-neutralizing or cross-protective antibodies. In addition, histological analysis showed reduced lung inflammation in vaccinated mice compared to that in unvaccinated controls following heterosubtypic challenge. This reduced inflammation was associated with enhanced early recruitment of T cells, both CD4+ and CD8+, and with early influenza virus-specific cytotoxic T-cell responses. Therefore, cross-protective immunity induced by vaccination with -irradiated influenza A virus is mediated mainly by Tc-cell responses.Yoichi Furuya, Jennifer Chan, Matthias Regner, Mario Lobigs, Aulikki Koskinen, Tuckweng Kok, Jim Manavis, Peng Li, Arno Müllbacher, and Mohammed Alsharif
Effect of inactivation method on the cross-protective immunity induced by whole 'killed' influenza A viruses and commercial vaccine preparations
No full textWe have recently shown that intranasal (i.n.) administration of {gamma}-irradiated A/PR/8 [A/Puerto Rico/8/34 (H1N1)] protects mice against lethal avian influenza A/Vietnam/1203/2004 (H5N1) and other heterosubtypic influenza A infections. Here, we used {gamma}-irradiated, formalin- and UV-inactivated A/PC [A/Port Chalmers/1/73 (H3N2)] virus preparations and compared their ability to induce both homologous and heterosubtypic protective immunity. Our data show that, in contrast to i.n. vaccination with formalin- or UV-inactivated virus, or the present commercially available trivalent influenza vaccine, a single dose of {gamma}-ray-inactivated A/PC ({gamma}-A/PC) conferred significant protection in mice against both homologous and heterosubtypic virus challenges. A multiple immunization regime was required for formalin-inactivated virus preparations to induce protective immunity against a homotypic virus challenge, but did not induce influenza A strain cross-protective immunity. The highly immunogenic {gamma}-A/PC, but not formalin- or UV-inactivated A/PC, nor the currently available subvirion vaccine, elicited cytotoxic T-cell responses that are most likely responsible for the cross-protective and long-lasting immunity against highly lethal influenza A infections in mice. Finally, freeze-drying of {gamma}-A/PC did not affect the ability to induce cross-protective immunity.Yoichi Furuya, Matthias Regner, Mario Lobigs, Aulikki Koskinen, Arno Müllbacher and Mohammed Alsharif
Gamma-irradiated influenza virus uniquely induces IFN-I mediated lymphocyte activation independent of the TLR7/MyD88 pathway
No full textBackground: We have shown previously in mice, that infection with live viruses, including influenza/A and Semliki Forest virus (SFV), induces systemic partial activation of lymphocytes, characterized by cell surface expression of CD69 and CD86, but not CD25. This partial lymphocytes activation is mediated by type-I interferons (IFN-I). Importantly, we have shown that c-irradiated SFV does not induce IFN-I and the associated lymphocyte activation. Principal Findings: Here we report that, in contrast to SFV, c-irradiated influenza A virus elicits partial lymphocyte activation in vivo. Furthermore, we show that when using influenza viruses inactivated by a variety of methods (UV, ionising radiation and formalin treatment), as well as commercially available influenza vaccines, only c-irradiated influenza virus is able to trigger IFN-I-dependent partial lymphocyte activation in the absence of the TLR7/MyD88 signalling pathways. Conclusions: Our data suggest an important mechanism for the recognition of c-irradiated influenza vaccine by cytosolic receptors, which correspond with the ability of c-irradiated influenza virus to induce cross-reactive and cross-protective cytotoxic T cell responses.Yoichi Furuya, Jennifer Chan, En-Chi Wan, Aulikki Koskinen, Kerrilyn R. Diener, John D. Hayball, Matthias Regner, Arno Müllbacher, Mohammed Alsharif
Granzymes in cytolytic lymphocytes to kill a killer?
No full textGranzymes (gzm) are major components of the granules of cytolytic lymphocytes, natural killer and cytotoxic T cells. Their generally accepted mode of action consists of their directed secretion towards a virus-infected or neoplastic target cell and perforin-dependent delivery to the target cell cytosol, where they engage in various actions resulting in target cell apoptosis. Here, based on observations of infection of gzmAxB-/- mice with ectromelia virus, mousepox, we propose an additional - and distinct - function for gzmA and B. In this model, gzm constitute one of the first lines of defence of immune cells against virus infection of immune cells themselves. Accordingly, endogenous gzm interfere with viral replication in cytolytic lymphocytes either directly, as a result of their proteolytic activity, leading to destruction of viral proteins, or indirectly, via: (i) processes akin to the caspase cascade when acting as effector molecules in the induction of target cell apoptosis; or (ii) their capacity to induce early inflammatory mediators. We discuss the predictions of the model in the light of available data
- …
