scholarly journals The SARS-CoV-2 Omicron (B.1.1.529) variant exhibits altered pathogenicity, transmissibility, and fitness in the golden Syrian hamster model

2022 ◽  
Author(s):  
Shuofeng Yuan ◽  
Zi-Wei Ye ◽  
Ronghui Liang ◽  
Kaiming Tang ◽  
Anna Jinxia Zhang ◽  
...  
Keyword(s):  
Syrian Hamster ◽  
Neutralizing Antibodies ◽  
Selection Pressure ◽  
Immune Selection ◽  
Hamster Model ◽  
Golden Syrian Hamster ◽  
New Variant ◽  
Contact Transmission

The newly emerging SARS-CoV-2 Omicron (B.1.1.529) variant first identified in South Africa in November 2021 is characterized by an unusual number of amino acid mutations in its spike that renders existing vaccines and therapeutic monoclonal antibodies dramatically less effective. The in vivo pathogenicity, transmissibility, and fitness of this new Variant of Concerns are unknown. We investigated these virological attributes of the Omicron variant in comparison with those of the currently dominant Delta (B.1.617.2) variant in the golden Syrian hamster COVID-19 model. Omicron-infected hamsters developed significantly less body weight losses, clinical scores, respiratory tract viral burdens, cytokine/chemokine dysregulation, and tissue damages than Delta-infected hamsters. The Omicron and Delta variant were both highly transmissible (100% vs 100%) via contact transmission. Importantly, the Omicron variant consistently demonstrated about 10-20% higher transmissibility than the already-highly transmissible Delta variant in repeated non-contact transmission studies (overall: 30/36 vs 24/36, 83.3% vs 66.7%). The Delta variant displayed higher fitness advantage than the Omicron variant without selection pressure in both in vitro and in vivo competition models. However, this scenario drastically changed once immune selection pressure with neutralizing antibodies active against the Delta variant but poorly active against the Omicron variant were introduced, with the Omicron variant significantly outcompeting the Delta variant. Taken together, our findings demonstrated that while the Omicron variant is less pathogenic than the Delta variant, it is highly transmissible and can outcompete the Delta variant under immune selection pressure. Next-generation vaccines and antivirals effective against this new VOC are urgently needed.

scholarly journals The HtrA-Like Protease CD3284 Modulates Virulence of Clostridium difficile

2014 ◽  
Vol 82 (10) ◽  
pp. 4222-4232 ◽  
Author(s):  
Dennis Bakker ◽  
Anthony M. Buckley ◽  
Anne de Jong ◽  
Vincent J. C. van Winden ◽  
Joost P. A. Verhoeks ◽  
...  
Keyword(s):  
Clostridium Difficile ◽  
Virulence Factors ◽  
Pathogenic Bacteria ◽  
Microarray Data Analysis ◽  
Toxin A ◽  
Hamster Model ◽  
Golden Syrian Hamster ◽  
Content Type

ABSTRACTIn the past decade,Clostridium difficilehas emerged as an important gut pathogen. Symptoms ofC. difficileinfection range from mild diarrhea to pseudomembranous colitis. Besides the two main virulence factors toxin A and toxin B, other virulence factors are likely to play a role in the pathogenesis of the disease. In other Gram-positive and Gram-negative pathogenic bacteria, conserved high-temperature requirement A (HtrA)-like proteases have been shown to have a role in protein homeostasis and quality control. This affects the functionality of virulence factors and the resistance of bacteria to (host-induced) environmental stresses. We found that theC. difficile630 genome encodes a single HtrA-like protease (CD3284; HtrA) and have analyzed its rolein vivoandin vitrothrough the creation of an isogenic ClosTron-basedhtrAmutant ofC. difficilestrain 630Δerm(wild type). In contrast to the attenuated phenotype seen withhtrAdeletion in other pathogens, this mutant showed enhanced virulence in the Golden Syrian hamster model of acuteC. difficileinfection. Microarray data analysis showed a pleiotropic effect ofhtrAon the transcriptome ofC. difficile, including upregulation of the toxin A gene. In addition,the htrAmutant showed reduced spore formation and adherence to colonic cells. Together, our data show thathtrAcan modulate virulence inC. difficile.

scholarly journals Persimmon-derived tannin has antiviral effects and reduces the severity of infection and transmission of SARS-CoV-2 in a Syrian hamster model

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Ryutaro Furukawa ◽  
Masahiro Kitabatake ◽  
Noriko Ouji-Sageshima ◽  
Yuki Suzuki ◽  
Akiyo Nakano ◽  
...  
Keyword(s):  
Oral Administration ◽  
Syrian Hamster ◽  
Carboxymethyl Cellulose ◽  
Plaque Assay ◽  
Control Group ◽  
Dependent Manner ◽  
Hamster Model ◽  
Antiviral Effects

AbstractCoronavirus disease 2019 (COVID-19) caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has rapidly spread across the world. Inactivating the virus in saliva and the oral cavity represents a reasonable approach to prevent human-to-human transmission because the virus is easily transmitted through oral routes by dispersed saliva. Persimmon-derived tannin is a condensed type of tannin that has strong antioxidant and antimicrobial activity. In this study, we investigated the antiviral effects of persimmon-derived tannin against SARS-CoV-2 in both in vitro and in vivo models. We found that persimmon-derived tannin suppressed SARS-CoV-2 titers measured by plaque assay in vitro in a dose- and time-dependent manner. We then created a Syrian hamster model by inoculating SARS-CoV-2 into hamsters’ mouths. Oral administration of persimmon-derived tannin dissolved in carboxymethyl cellulose before virus inoculation dramatically reduced the severity of pneumonia with lower virus titers compared with a control group inoculated with carboxymethyl cellulose alone. In addition, pre-administration of tannin to uninfected hamsters reduced hamster-to-hamster transmission of SARS-CoV-2 from a cohoused, infected donor cage mate. These data suggest that oral administration of persimmon-derived tannin may help reduce the severity of SARS-CoV-2 infection and transmission of the virus.

scholarly journals Surgical Mask Partition Reduces the Risk of Noncontact Transmission in a Golden Syrian Hamster Model for Coronavirus Disease 2019 (COVID-19)

2020 ◽  
Vol 71 (16) ◽  
pp. 2139-2149 ◽  
Author(s):  
Jasper Fuk-Woo Chan ◽  
Shuofeng Yuan ◽  
Anna Jinxia Zhang ◽  
Vincent Kwok-Man Poon ◽  
Chris Chung-Sing Chan ◽  
...  
Keyword(s):  
Experimental Evidence ◽  
Syrian Hamster ◽  
Antigen Expression ◽  
Hamster Model ◽  
Golden Syrian Hamster ◽  
Healthcare Settings ◽  
Clinical Scoring ◽  
Respiratory Droplets ◽  
Viral Nucleocapsid

Abstract Background Coronavirus disease 2019 (COVID-19) caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is believed to be mostly transmitted by medium- to large-sized respiratory droplets, although airborne transmission may be possible in healthcare settings involving aerosol-generating procedures. Exposure to respiratory droplets can theoretically be reduced by surgical mask usage. However, there is a lack of experimental evidence supporting surgical mask usage for prevention of COVID-19. Methods We used a well-established golden Syrian hamster SARS-CoV-2 model. We placed SARS-CoV-2-challenged index hamsters and naive hamsters into closed system units each comprising 2 different cages separated by a polyvinyl chloride air porous partition with unidirectional airflow within the isolator. The effect of a surgical mask partition placed between the cages was investigated. Besides clinical scoring, hamster specimens were tested for viral load, histopathology, and viral nucleocapsid antigen expression. Results Noncontact transmission was found in 66.7% (10/15) of exposed naive hamsters. Surgical mask partition for challenged index or naive hamsters significantly reduced transmission to 25% (6/24, P = .018). Surgical mask partition for challenged index hamsters significantly reduced transmission to only 16.7% (2/12, P = .019) of exposed naive hamsters. Unlike the severe manifestations of challenged hamsters, infected naive hamsters had lower clinical scores, milder histopathological changes, and lower viral nucleocapsid antigen expression in respiratory tract tissues. Conclusions SARS-CoV-2 could be transmitted by respiratory droplets or airborne droplet nuclei which could be reduced by surgical mask partition in the hamster model. This is the first in vivo experimental evidence to support the possible benefit of surgical mask in prevention of COVID-19 transmission, especially when masks were worn by infected individuals.

scholarly journals Discovery and Development of Human SARS-CoV-2 Neutralizing Antibodies using an Unbiased Phage Display Library Approach

2020 ◽  
Author(s):  
Xia Cao ◽  
Junki Maruyama ◽  
Heyue Zhou ◽  
Lisa Kerwin ◽  
Rachel Sattler ◽  
...  
Keyword(s):  
Phage Display ◽  
Neutralizing Antibodies ◽  
Phage Display Library ◽  
Antibody Library ◽  
Hamster Model ◽  
Functional Profiling ◽  
Dose Dependent ◽  
Potent Protection

ABSTRACTSARS-CoV-2 neutralizing antibodies represent an important component of the ongoing search for effective treatment of and protection against COVID-19. We report here on the use of a naïve phage display antibody library to identify a panel of fully human SARS-CoV-2 neutralizing antibodies. Following functional profiling in vitro against an early pandemic isolate as well as a recently emerged isolate bearing the D614G Spike mutation, the clinical candidate antibody, STI-1499, and the affinity-engineered variant, STI-2020, were evaluated for in vivo efficacy in the Syrian golden hamster model of COVID-19. Both antibodies demonstrated potent protection against the pathogenic effects of the disease and a dose-dependent reduction of virus load in the lungs, reaching undetectable levels following a single dose of 500 micrograms of STI-2020. These data support continued development of these antibodies as therapeutics against COVID-19 and future use of this approach to address novel emerging pandemic disease threats.

scholarly journals Nebulized delivery of a broadly neutralizing SARS-CoV-2 RBD-specific nanobody prevents clinical, virological and pathological disease in a Syrian hamster model of COVID-19

2021 ◽  
Author(s):  
Thomas J Esparza ◽  
Yaozong Chen ◽  
Negin P Martin ◽  
Helle Bielefeldt-Ohmann ◽  
Richard A Bowen ◽  
...  
Keyword(s):  
Syrian Hamster ◽  
Low Cost ◽  
Unmet Need ◽  
Lung Pathology ◽  
Hamster Model ◽  
Angiotensin Converting Enzyme 2 ◽  
In Vitro Characterization ◽  
Pathological Disease

There remains an unmet need for globally deployable, low-cost therapeutics for the ongoing severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) pandemic. Previously, we reported on the isolation and in vitro characterization of a potent single-domain nanobody, NIH-CoVnb-112, specific for the receptor binding domain (RBD) of SARS-CoV-2. Here, we report on the molecular basis for the observed broad in vitro neutralization capability of NIH-CoVnb-112 against variant SARS-CoV-2 pseudoviruses, including the currently dominant Delta variant. The structure of NIH-CoVnb-112 bound to SARS-CoV-2 RBD reveals a large contact surface area overlapping the angiotensin converting enzyme 2 (ACE2) binding site, which is largely unencumbered by the common RBD mutations. In an in vivo pilot study, we demonstrate effective reductions in weight loss, viral burden, and lung pathology in a Syrian hamster model of COVID-19 following nebulized delivery of NIH-CoVnb-112. These findings support the further development of NIH-CoVnb-112 as a potential adjunct preventative therapeutic for the treatment of SARS-CoV-2 infection.

scholarly journals Pharmacological, Toxicological, and Dose Range Assessment of OG716, a Novel Lantibiotic for the Treatment ofClostridium difficile-Associated Infection

2019 ◽  
Vol 63 (4) ◽  
Author(s):  
Mark E. Pulse ◽  
William J. Weiss ◽  
Johan A. Kers ◽  
Anthony W. DeFusco ◽  
Jae H. Park ◽  
...  
Keyword(s):  
Clostridium Difficile ◽  
Dose Range ◽  
Hamster Model ◽  
Ofclostridium Difficile ◽  
Golden Syrian Hamster ◽  
Content Type ◽  
Lead Compounds ◽  
Novel Antibiotics

ABSTRACTLantibiotics present an attractive scaffold for the development of novel antibiotics. We report here a novel lantibiotic for the treatment ofClostridium difficileinfection. The lead compounds were selected from a library of over 700 single- and multiple-substitution variants of the lantibiotic mutacin 1140 (MU1140). The best performersin vitroandin vivowere further used to challenge Golden Syrian hamsters orally in a Golden Syrian hamster model ofClostridium difficile-associated disease (CDAD) in a dose-response format, resulting in the selection of OG716 as the lead compound. This lantibiotic was characterized by a 50% effective dose of 23.85 mg/kg of body weight/day (10.97 μmol/kg/day) in this model. Upon oral administration of the maximum feasible dose (≥1,918 mg/kg/day), no observable toxicities or side effects were noted, and no effect on intestinal motility was observed. Compartmentalization to the gastrointestinal tract was confirmed. MU1140-derived variants offer a large pipeline for the development of novel antibiotics for the treatment of several indications and are particularly attractive considering their novel mechanism of action. Based on the currently available data, OG716 has an acceptable profile for further development for the treatment of CDAD.

scholarly journals A single dose of recombinant VSV-ΔG-spike vaccine provides protection against SARS-CoV-2 challenge

2020 ◽  
Author(s):  
Yfat Yahalom-Ronen ◽  
Hadas Tamir ◽  
Sharon Melamed ◽  
Boaz Politi ◽  
Ohad Shifman ◽  
...  
Keyword(s):  
Single Dose ◽  
Neutralizing Antibodies ◽  
Rapid Development ◽  
Body Weight Loss ◽  
Spike Protein ◽  
Effective Vaccine ◽  
Lung Pathology ◽  
Golden Syrian Hamster

AbstractThe COVID-19 pandemic caused by SARS-CoV-2 that emerged in December 2019 in China resulted in over 7.8 million infections and over 430,000 deaths worldwide, imposing an urgent need for rapid development of an efficient and cost-effective vaccine, suitable for mass immunization. Here, we generated a replication competent recombinant VSV-ΔG-spike vaccine, in which the glycoprotein of VSV was replaced by the spike protein of the SARS-CoV-2. In vitro characterization of the recombinant VSV-ΔG-spike indicated expression and presentation of the spike protein on the viral membrane with antigenic similarity to SARS-CoV-2. A golden Syrian hamster in vivo model for COVID-19 was implemented. We show that vaccination of hamsters with recombinant VSV-ΔG-spike results in rapid and potent induction of neutralizing antibodies against SARS-CoV-2. Importantly, single-dose vaccination was able to protect hamsters against SARS-CoV-2 challenge, as demonstrated by the abrogation of body weight loss of the immunized hamsters compared to unvaccinated hamsters. Furthermore, whereas lungs of infected hamsters displayed extensive tissue damage and high viral titers, immunized hamsters’ lungs showed only minor lung pathology, and no viral load. Taken together, we suggest recombinant VSV-ΔG-spike as a safe, efficacious and protective vaccine against SARS-CoV-2 infection.

scholarly journals A single dose of recombinant VSV-∆G-spike vaccine provides protection against SARS-CoV-2 challenge

2020 ◽  
Vol 11 (1) ◽  
Author(s):  
Yfat Yahalom-Ronen ◽  
Hadas Tamir ◽  
Sharon Melamed ◽  
Boaz Politi ◽  
Ohad Shifman ◽  
...  
Keyword(s):  
Single Dose ◽  
Neutralizing Antibodies ◽  
Rapid Development ◽  
Body Weight Loss ◽  
Spike Protein ◽  
Effective Vaccine ◽  
In Vivo Model ◽  
Golden Syrian Hamster

AbstractThe COVID-19 pandemic caused by SARS-CoV-2 imposes an urgent need for rapid development of an efficient and cost-effective vaccine, suitable for mass immunization. Here, we show the development of a replication competent recombinant VSV-∆G-spike vaccine, in which the glycoprotein of VSV is replaced by the spike protein of SARS-CoV-2. In-vitro characterization of this vaccine indicates the expression and presentation of the spike protein on the viral membrane with antigenic similarity to SARS-CoV-2. A golden Syrian hamster in-vivo model for COVID-19 is implemented. We show that a single-dose vaccination results in a rapid and potent induction of SARS-CoV-2 neutralizing antibodies. Importantly, vaccination protects hamsters against SARS-CoV-2 challenge, as demonstrated by the abrogation of body weight loss, and  alleviation of the extensive tissue damage and viral loads in lungs and nasal turbinates. Taken together, we suggest the recombinant VSV-∆G-spike as a safe, efficacious and protective vaccine against SARS-CoV-2.

scholarly journals Protective Effects of STI-2020 Antibody Delivered Post-Infection by the Intranasal or Intravenous Route in a Syrian Golden Hamster COVID-19 Model

2020 ◽  
Author(s):  
Yanwen Fu ◽  
Junki Maruyama ◽  
Alok Singh ◽  
Reyna Lim ◽  
Arthur Ledesma ◽  
...  
Keyword(s):  
Lung Tissue ◽  
Post Infection ◽  
Neutralizing Antibodies ◽  
In Vivo Studies ◽  
Intravenous Route ◽  
Protective Effects ◽  
Antibody Treatment ◽  
Hamster Model

ABSTRACTWe have previously reported that the SARS-CoV-2 neutralizing antibody, STI-2020, potently inhibits cytopathic effects of infection by genetically diverse clinical SARS-CoV-2 pandemic isolates in vitro, and has demonstrated efficacy in a hamster model of COVID-19 when administered by the intravenous route immediately following infection. We now have extended our in vivo studies of STI-2020 to include disease treatment efficacy, profiling of biodistribution of STI-2020 in mice when antibody is delivered intranasally (IN) or intravenously (IV), as well as pharmacokinetics in mice following IN antibody administration. Importantly, SARS-CoV-2-infected hamsters were treated with STI-2020 using these routes, and treatment effects on severity and duration of COVID-19-like disease in this model were evaluated. In SARS-CoV-2 infected hamsters, treatment with STI-2020 12 hours post-infection using the IN route led to a decrease in severity of clinical disease signs and a more robust recovery during 9 days of infection as compared to animals treated with an isotype control antibody. Treatment via the IV route using the same dose and timing regimen resulted in a decrease in the average number of consecutive days that infected animals experienced weight loss, shortening the duration of disease and allowing recovery to begin more rapidly in STI-2020 treated animals. Following IN administration in mice, STI-2020 was detected within 10 minutes in both lung tissue and lung lavage. The half-life of STI-2020 in lung tissue is approximately 25 hours. We are currently investigating the minimum effective dose of IN-delivered STI-2020 in the hamster model as well as establishing the relative benefit of delivering neutralizing antibodies by both IV and IN routes.

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