Examinando por Autor "Mora, Jorge E."

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    Evaluation of monoclonal antibodies that detect conserved proteins from Respiratory Syncytial Virus, Metapneumovirus and Adenovirus in human samples
    (Elsevier B.V., 2018-04) González, Liliana A.; Vázquez, Yaneisi; Mora, Jorge E.; Palavecino, Christian E.; Bertrand, Pablo; Ferrés, Marcela; Contreras, Ana M.; Beckhaus, Andrea A.; Riedel, Claudia; Bueno, Susan M.
    Human Respiratory Syncytial Virus (hRSV), human Metapneumovirus (hMPV) and Adenovirus (ADV), are three of the most prevalent viruses responsible for pneumonia and bronchiolitis in children and elderly worldwide, accounting for a high number of hospitalizations annually. Diagnosis of these viruses is required to take clinical actions that allow an appropriate patient management. Thereby, new strategies to design fast diagnostic methods are highly required. In the present work, six monoclonal antibodies (mAbs, two for each virus) specific for conserved proteins from hRSV, hMPV and ADV were generated and evaluated through different immunological techniques, based on detection of purified protein, viral particles and human samples. In vitro evaluation of these antibodies showed higher specificity and sensitivity than commercial antibodies tested in this study. These antibodies were used to design a sandwich ELISA tests that allowed the detection of hRSV, hMPV, and ADV in human nasopharyngeal swabs. We observed that hRSV and ADV were detected with sensitivity and specificity equivalent to a current Direct Fluorescence Assay (DFA) methodology. However, hMPV was detected with more sensitivity than DFA. Our data suggest that these new mAbs can efficiently identify infected samples and discriminate from patients infected with other respiratory pathogens. © 2018 The Authors
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    Protective T cell immunity against respiratory syncytial virus is efficiently induced by recombinant BCG
    (National Academy of Sciences, 2008-12-30) Bueno, Susan M.; González, Pablo A.; Cautivo, Kelly M.; Mora, Jorge E.; Leiva, Eduardo D.; Tobar, Hugo E.; Fennelly, Glenn J.; Eugenin, Eliseo A.; Jacobs Jr., William R.; Riedel, Claudia A.; Kalergis, Alexis M.
    Respiratory syncytial virus (RSV) is one of the leading causes of childhood hospitalization and a major health burden worldwide. Unfortunately, because of an inefficient immunological memory, RSV infection provides limited immune protection against reinfection. Furthermore, RSV can induce an inadequate Th2-type immune response that causes severe respiratory tract inflammation and obstruction. It is thought that effective RSV clearance requires the induction of balanced Th1-type immunity, involving the activation of IFN-γ-secreting cytotoxic T cells. A recognized inducer of Th1 immunity is Mycobacterium bovis bacillus Calmette-Guérin (BCG), which has been used in newborns for decades in several countries as a tuberculosis vaccine. Here, we show that immunization with recombinant BCG strains expressing RSV antigens promotes protective Th1-type immunity against RSV in mice. Activation of RSV-specific T cells producing IFN-γ and IL-2 was efficiently obtained after immunization with recombinant BCG. This type of T cell immunity was protective against RSV challenge and caused a significant reduction of inflammatory cell infiltration in the airways. Furthermore, mice immunized with recombinant BCG showed no weight loss and reduced lung viral loads. These data strongly support recombinant BCG as an efficient vaccine against RSV because of its capacity to promote protective Th1 immunity. © 2008 by The National Academy of Sciences of the USA.
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    Surface expression of the hRSV nucleoprotein impairs immunological synapse formation with T cells
    (National Academy of Sciences, 2014-08) Céspedes, Pablo F.; Bueno, Susan M.; Gomez, Roberto S.; Riquelme, Sebastián A.; Palavecino, Christian E.; Mackern-Oberti, Juan Pablo; Mora, Jorge E.; Depoil, David; Sacristań, Catarina; Cammer, Michael; Creneguy, Alison; Nguyen, Tuan H.; Riedel, Claudia A.; Dustin, Michael L.; Kalergis, Alexis M.
    Human respiratory syncytial virus (hRSV) is the leading cause of bronchiolitis and pneumonia in young children worldwide. The recurrent hRSV outbreaks and reinfections are the cause of a significant public health burden and associate with an inefficient antiviral immunity, even after disease resolution. Although several mouse- and human cell-based studies have shown that hRSV infection prevents naïve T-cell activation by antigen-presenting cells, the mechanism underlying such inhibition remains unknown. Here, we show that the hRSV nucleoprotein (N) could be at least partially responsible for inhibiting T-cell activation during infection by this virus. Early after infection, the N protein was expressed on the surface of epithelial and dendritic cells, after interacting with trans-Golgi and lysosomal compartments. Further, experiments on supported lipid bilayers loaded with peptide-MHC (pMHC) complexes showed that surface-anchored N protein prevented immunological synapse assembly by naive CD4+ T cells and, to a lesser extent, by antigen-experienced T-cell blasts. Synapse assembly inhibition was in part due to reduced T-cell receptor (TCR) signaling and pMHC clustering at the T-cell−bilayer interface, suggesting that N protein interferes with pMHC−TCR interactions. Moreover, N protein colocalized with the TCR independently of pMHC, consistent with a possible interaction with TCR complex components. Based on these data, we conclude that hRSV N protein expression at the surface of infected cells inhibits T-cell activation. Our study defines this protein as a major virulence factor that contributes to impairing acquired immunity and enhances susceptibility to reinfection by hRSV.