Project description:Emerging infectious diseases pose a significant threat to both human and animal populations. Rapid de novo identification of protective antigens from a clinical isolate and development of an antigen-matched vaccine is a golden strategy to prevent the spread of emerging novel pathogens. Here, we have developed a universal pipeline by integrating proteosurfaceomics, secretomics, and BacScan technologies for the rapid de novo identification of bacterial protective proteins from a clinical isolate without prior knowledge of the pathogenic bacterium. As a proof of concept, we identified 3 novel protective proteins of A. pleuropneumoniae. Using the protective protein HBS1_14 and toxin proteins, we have developed a promising multivalent subunit vaccine against A. pleuropneumoniae. We believe that our strategy can be applied to any bacterial pathogen and has the potential to significantly accelerate the development of antigen-matched vaccines to prevent the spread of an emerging novel bacterial pathogen.
Project description:Spaceflight uniquely alters the physiology of both human cells and microbial pathogens, stimulating cellular and molecular changes directly relevant to infectious disease. However, the influence of this environment on host-pathogen interactions remains poorly understood. Here we report our results from the STL-IMMUNE pilot study flown aboard STS-131, which investigated multi-omic responses (transcriptomic, proteomic) of human intestinal epithelial cells to infection with Salmonella Typhimurium when both host and pathogen were simultaneously exposed to spaceflight. To our knowledge, this is the first in vitro in-flight infection and dual RNA-seq analysis using human cells.
Project description:The COVID-19 pandemic has unveiled an urgent need for new anti-virals to control emerging infectious diseases and potential future pandemics. Classic anti-virals are currently designed to directly interfere with pathogens. However, anti-virals are often insufficient to rapidly clear infections in the absence of an effective immune response. Immunotherapy could complement the use of anti-virals, however its application to infectious diseases remains largely unexplored. In this work, we found that the anti-viral drug remdesivir has previously unknown immunomodulatory properties which contribute to its therapeutic effect against SARS-CoV-2. These properties are due to remdesivir metabolite, GS-441524, acting as an Adenosine A2A Receptor antagonist, a function that is distinct from its intrinsic anti-viral activity. Our findings support a new rationale for the design of next-generation anti-viral agents with dual – immunomodulatory and intrinsic - anti-viral properties. These compounds could represent game-changing therapies to control emerging viral diseases and future pandemics.
Project description:Streptococcus suis serotype 2 (SS2), a major swine pathogen and an emerging zoonotic agent, has greatly challenged global public health. Systematical information about host immune response to the infection is important for understanding the molecular mechanism of diseases. Here, we investigated the global expression changes in spleen following SS2 infection using the Affymetrix Porcine Genechip. Our findings indicate previously unrecognized gene transcription changes in case of SS infection in vivo. Our data should provide new clues for immune response in mammals and identification of candidate genes related to SS resistance.
