Virus-like particles (VLPs) offer great potential as a safe and effective vaccine platform against SARS-CoV-2, the causative agent of COVID-19. Here, we show that SARS-CoV-2 VLPs can be generated by expression of the four viral structural proteins in a mammalian expression system. Immunization of mice with a monovalent VLP vaccine elicited a potent humoral response, showing neutralizing activity against multiple variants of SARS-CoV-2. Subsequent immunogenicity and efficacy studies were performed in the Golden Syrian hamster model, which closely resembles the pathology and progression of COVID-19 in humans. Hamsters immunized with a bivalent VLP vaccine were significantly protected from infection with the Beta or Delta variant of SARS-CoV-2. Vaccinated hamsters showed reduced viral load, shedding, replication, and pathology in the respiratory tract. Immunized hamsters also showed variable levels of cross-neutralizing activity against the Omicron variant. Overall, the VLP vaccine elicited robust protective efficacy against SARS-CoV-2. These promising results warrant further study of multivalent VLP vaccines in Phase I clinical trials in humans.
Sepsis, a life‐threatening clinical condition affecting more than 1.5 million Americans per year, is defined as an over‐exuberant immune response to infection. Currently, sepsis is the leading cause of death in U.S. hospitals, and the incidence of sepsis caused by Gram‐negative bacteria, such as Escherichia coli (E. coli), has been steadily increasing since the late 1990's. While the detailed mechanism of sepsis is not fully understood, several bacterial components are thought to contribute to the hyper‐inflammatory response in humans. Past studies suggest that one E. coli lipoprotein, Peptidoglycan‐Associated Lipoprotein (Pal), may contribute to inflammation and the pathogenesis of sepsis. This work describes our efforts to elucidate the role of Pal in E. coli sepsis and the effect of antibiotics in Pal release from E. coli using a mouse model of sepsis. Our preliminary results corroborate the hypothesis that Pal releases from E. coli and contributes to inflammation and sepsis.Support or Funding InformationRochester Institute of TechnologyThis abstract is from the Experimental Biology 2019 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.
Sepsis can result from a systemic bacterial infection, followed by an over‐exuberant immune response, which leads to widespread inflammation. Severe sepsis can result in organ failure and in severe cases, death. Past studies have proposed a role for bacterial Peptidoglycan‐Associated Lipoprotein (Pal) in the pathogenesis of Gram‐negative bacterial sepsis. In this study, we confirmed that Pal is released from Gram‐negative bacteria, Escherichia coli (E. coli), under certain culture conditions, including in the presence of certain antibiotics. Our preliminary results suggest that different antibiotics have differential effects on Pal’s release from E.coli. Since the majority of sepsis patients are administered antibiotics, our findings may be of great significance to the medical field and the sepsis research community.
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RIT FEAD/DRIG and NIH Bootcamp , RIT LSAMP program, Dr. Michael Pichichero Rochester General Hospital Research Institute
The clinical condition of sepsis often results from a systemic bacterial infection, followed by an over‐exuberant immune response, which leads to widespread inflammation. Severe sepsis can result in organ failure or death. Past studies have proposed a role for bacterial Peptidoglycan‐Associated Lipoprotein (Pal) in the pathogenesis of Gram‐negative sepsis. In this study, we confirmed the ability of Escherichia coli (E. coli) to release Pal under certain conditions, and we employed both in vitro and in vivo (mouse) studies and protein detection methods to determine the effect of antibiotics on Pal's release from E. coli. Results from our studies suggest that antibiotics that target peptidoglycan may enhance Pal's release more so than other antibiotics.Support or Funding InformationRochester Institute of TechnologyThis abstract is from the Experimental Biology 2019 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.
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