Middle East respiratory syndrome (MERS) represents an important respiratory disease accompanied by lethal outcome in one third of human patients. In recent years, several investigators developed protective antibodies which could be used as prophylaxis in prospective human epidemics. In the current study, eight human monoclonal antibodies (mAbs) with neutralizing and non-neutralizing capabilities, directed against different epitopes of the MERS-coronavirus (MERS-CoV) spike (MERS-S) protein, were investigated with regard to their ability to immunohistochemically detect respective epitopes on formalin-fixed paraffin-embedded (FFPE) nasal tissue sections of MERS-CoV experimentally infected alpacas. The most intense immunoreaction was detected using a neutralizing antibody directed against the receptor binding domain S1B of the MERS-S protein, which produced an immunosignal in the cytoplasm of ciliated respiratory epithelium and along the apical membranous region. A similar staining was obtained by two other mAbs which recognize the sialic acid-binding domain and the ectodomain of the membrane fusion subunit S2, respectively. Five mAbs lacked immunoreactivity for MERS-CoV antigen on FFPE tissue, even though they belong, at least in part, to the same epitope group. In summary, three tested human mAbs demonstrated capacity for detection of MERS-CoV antigen on FFPE samples and may be implemented in double or triple immunohistochemical methods.
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http://dx.doi.org/10.1016/j.vetimm.2019.109939 | DOI Listing |
J Virol
December 2024
State Key Laboratory of Virology, Taikang Center for Life and Medical Sciences, College of Life Sciences, Wuhan University, Wuhan, China.
Unlabelled: Viral immunosuppression substantially affects the host immune response of infected patients and the protective efficacy of vaccines. Here, we found that the spike (S) protein, the major vaccine antigen of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), strongly suppresses host innate immunity by inhibiting interferon-stimulated gene (ISG) expression through both S1 and S2 subunits. Mechanistically, the S protein inhibited the formation of the classic interferon-stimulated gene factor 3 (ISGF3) complex composed of STAT1, STAT2, and IRF9 by competing with STAT2 for binding to IRF9, thereby impeding the transcription of ISGs.
View Article and Find Full Text PDFFront Immunol
December 2024
Shanghai Public Health Clinical Center and Institutes of Biomedical Sciences, Fudan University, Shanghai, China.
Introduction: Coronaviruses and influenza viruses are significant respiratory pathogens that cause severe disease burdens and economic losses for society. Due to their diversity and evolution, vaccines typically require periodic updating to remain effective. An additional challenge is imposed by the possible coinfection of SARS-CoV-2 and influenza, which could increase disease severity.
View Article and Find Full Text PDFCell Rep
December 2024
Institute for Protein Design, University of Washington, Seattle, WA 98195, USA; Department of Biochemistry, University of Washington, Seattle, WA 98195, USA. Electronic address:
Middle East respiratory syndrome coronavirus (MERS-CoV) is a betacoronavirus that causes severe respiratory illness in humans. There are no licensed vaccines against MERS-CoV and only a few candidates in phase I clinical trials. Here, we develop MERS-CoV vaccines utilizing a computationally designed protein nanoparticle platform that has generated safe and immunogenic vaccines against various enveloped viruses, including a licensed vaccine for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2).
View Article and Find Full Text PDFbioRxiv
November 2024
Department of Biochemistry, University of Washington, Seattle, WA 98195, USA.
PLoS Pathog
November 2024
College of Life Sciences, Nanjing Agricultural University, Nanjing, China.
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