scholarly journals Simulation of the Clinical and Pathological Manifestations of Coronavirus Disease 2019 (COVID-19) in a Golden Syrian Hamster Model: Implications for Disease Pathogenesis and Transmissibility

2020 ◽  
Author(s):  
Jasper Fuk-Woo Chan ◽  
Anna Jinxia Zhang ◽  
Shuofeng Yuan ◽  
Vincent Kwok-Man Poon ◽  
Chris Chung-Sing Chan ◽  
...  
Keyword(s):  
Weight Loss ◽  
Viral Load ◽  
Syrian Hamster ◽  
Clinical Signs ◽  
Neutralizing Antibody ◽  
Adaptive Mutation ◽  
Lung Pathology ◽  
Hamster Model ◽  
Golden Syrian Hamster ◽  
Virus Challenge

Abstract Background A physiological small-animal model that resembles COVID-19 with low mortality is lacking. Methods Molecular docking on the binding between angiotensin-converting enzyme 2 (ACE2) of common laboratory mammals and the receptor-binding domain of the surface spike protein of SARS-CoV-2 suggested that the golden Syrian hamster is an option. Virus challenge, contact transmission, and passive immunoprophylaxis studies were performed. Serial organ tissues and blood were harvested for histopathology, viral load and titer, chemokine/cytokine level, and neutralizing antibody titer. Results The Syrian hamster could be consistently infected by SARS-CoV-2. Maximal clinical signs of rapid breathing, weight loss, histopathological changes from the initial exudative phase of diffuse alveolar damage with extensive apoptosis to the later proliferative phase of tissue repair, airway and intestinal involvement with viral nucleocapsid protein expression, high lung viral load, and spleen and lymphoid atrophy associated with marked chemokine/cytokine activation were observed within the first week of virus challenge. The mean lung virus titer was between 105 and 107 TCID50/g. Challenged index hamsters consistently infected naive contact hamsters housed within the same cages, resulting in similar pathology but not weight loss. All infected hamsters recovered and developed mean serum neutralizing antibody titers ≥1:427 14 days postchallenge. Immunoprophylaxis with early convalescent serum achieved significant decrease in lung viral load but not in lung pathology. No consistent nonsynonymous adaptive mutation of the spike was found in viruses isolated from the infected hamsters. Conclusions Besides satisfying Koch’s postulates, this readily available hamster model is an important tool for studying transmission, pathogenesis, treatment, and vaccination against SARS-CoV-2.

scholarly journals Absence of vaccine-enhanced disease with unexpected positive protection against SARS-CoV-2 by inactivated vaccine given within three days of virus challenge in Syrian hamster model

2021 ◽  
Author(s):  
Can Li ◽  
Yan-Xia Chen ◽  
Fei-Fei Liu ◽  
Andrew Chak-Yiu Lee ◽  
Yan Zhao ◽  
...  
Keyword(s):  
Syrian Hamster ◽  
Nucleocapsid Protein ◽  
Body Weight Loss ◽  
Neutralizing Antibody ◽  
Clinical Severity ◽  
Hamster Model ◽  
Golden Syrian Hamster ◽  
Nasal Turbinate ◽  
Virus Challenge ◽  
Disease Phenotypes

Abstract Background Mass vaccination against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is ongoing amidst widespread transmission during the Coronavirus Disease 2019 (COVID-19) pandemic. Disease phenotypes of SARS-CoV-2 exposure occurring around the time of vaccine administration have not been described. Methods Two-dose (14 days apart) vaccination regimen with a formalin-inactivated whole virion SARS-CoV-2 in golden Syrian hamster model was established. To investigate the disease phenotypes of a one-dose regimen given 3 days prior (D-3), 1 (D1) or 2 (D2) days after, or on the day (D0) of virus challenge, we monitored the serial clinical severity, tissue histopathology, virus burden, and antibody response of the vaccinated hamsters. Results The one-dose vaccinated hamsters had significantly lower clinical disease severity score, body weight loss, lung histology score, nucleocapsid protein expression in lung, infectious virus titres in the lung and nasal turbinate, inflammatory changes in intestines and a higher serum neutralizing antibody or IgG titre against the spike receptor-binding domain or nucleocapsid protein when compared to unvaccinated controls. These improvements were particularly noticeable in D-3, but also in D0, D1 and even D2 vaccinated hamsters to varying degrees. No increased eosinophilic infiltration was found in the nasal turbinate, lung, and intestine after virus challenge. Significantly higher serum titre of fluorescent foci microneutralization inhibition antibody was detected in D1 and D2 vaccinated hamsters at day 4 post-challenge compared to controls despite undetectable neutralizing antibody titre. Conclusions Vaccination just before or soon after exposure to SARS-CoV-2 does not worsen disease phenotypes and may even ameliorate infection.

scholarly journals Single-dose immunization with a chimpanzee adenovirus-based vaccine induces sustained and protective immunity against SARS-CoV-2 infection

2021 ◽  
Author(s):  
Linqi Zhang ◽  
Mingxi Li ◽  
Jingao Guo ◽  
Shuaiyao Lu ◽  
Runhong Zhou ◽  
...  
Keyword(s):  
Single Dose ◽  
Protective Immunity ◽  
Rhesus Macaques ◽  
Neutralizing Antibody ◽  
Effective Vaccine ◽  
High Dose ◽  
Lung Pathology ◽  
Protective Effects ◽  
Hamster Model ◽  
Golden Syrian Hamster

Abstract The development of an effective vaccine against SARS-CoV-2, the causative agent of pandemic coronavirus disease-2019 (COVID-19), is a global priority. Here, we present three chimpanzee adenovirus vaccines that express either the full-length spike (ChAdTS-S), or receptor-binding domain (RBD) with two different signal sequences (ChAdTS-RBD and ChAdTS-RBDs). Single-dose intranasal or intramuscular immunization induced robust and sustained neutralizing antibody responses in BALB/c mice, with ChAdTS-S being superior to ChAdTS-RBD and ChAdTS-RBDs. Intranasal immunization appeared to induce a predominately Th2-based response whereas intramuscular administration resulted in a predominately Th1 response. The neutralizing activity against several circulating SARS-CoV-2 variants remained unaffected for mice serum but reduced for rhesus macaque serum. Importantly, immunization with ChAdTS-S via either route induced protective immunity against high-dose challenge with live SARS-CoV-2 in rhesus macaques. Vaccinated macaques demonstrated dramatic decreases in viral RNA in the lungs and nasal swabs, as well as reduced lung pathology compared to the control animals. Similar protective effects were also found in a golden Syrian hamster model of SARS-CoV-2 infection. Taken together, these results confirm that ChAdTS-S can induce protective immune responses in experimental animals, meriting further development toward a human vaccine against SARS-CoV-2.

scholarly journals Single-Dose Immunization With a Chimpanzee Adenovirus-Based Vaccine Induces Sustained and Protective Immunity Against SARS-CoV-2 Infection

2021 ◽  
Vol 12 ◽  
Author(s):  
Mingxi Li ◽  
Jingao Guo ◽  
Shuaiyao Lu ◽  
Runhong Zhou ◽  
Hongyang Shi ◽  
...  
Keyword(s):  
Single Dose ◽  
Protective Immunity ◽  
Rhesus Macaques ◽  
Neutralizing Antibody ◽  
Effective Vaccine ◽  
High Dose ◽  
Lung Pathology ◽  
Protective Effects ◽  
Hamster Model ◽  
Golden Syrian Hamster

The development of a safe and effective vaccine against SARS-CoV-2, the causative agent of pandemic coronavirus disease-2019 (COVID-19), is a global priority. Here, we aim to develop novel SARS-CoV-2 vaccines based on a derivative of less commonly used rare adenovirus serotype AdC68 vector. Three vaccine candidates were constructed expressing either the full-length spike (AdC68-19S) or receptor-binding domain (RBD) with two different signal sequences (AdC68-19RBD and AdC68-19RBDs). Single-dose intramuscular immunization induced robust and sustained binding and neutralizing antibody responses in BALB/c mice up to 40 weeks after immunization, with AdC68-19S being superior to AdC68-19RBD and AdC68-19RBDs. Importantly, immunization with AdC68-19S induced protective immunity against high-dose challenge with live SARS-CoV-2 in a golden Syrian hamster model of SARS-CoV-2 infection. Vaccinated animals demonstrated dramatic decreases in viral RNA copies and infectious virus in the lungs, as well as reduced lung pathology compared to the control animals. Similar protective effects were also found in rhesus macaques. Taken together, these results confirm that AdC68-19S can induce protective immune responses in experimental animals, meriting further development toward a human vaccine against SARS-CoV-2.

scholarly journals BCX4430, a Novel Nucleoside Analog, Effectively Treats Yellow Fever in a Hamster Model

2014 ◽  
Vol 58 (11) ◽  
pp. 6607-6614 ◽  
Author(s):  
Justin G. Julander ◽  
Shanta Bantia ◽  
Brian R. Taubenheim ◽  
Dena M. Minning ◽  
Pravin Kotian ◽  
...  
Keyword(s):  
Weight Loss ◽  
Yellow Fever ◽  
Yellow Fever Virus ◽  
Neutralizing Antibody ◽  
Therapeutic Index ◽  
Nucleoside Analog ◽  
Hamster Model ◽  
Virus Challenge ◽  
Highly Active ◽  
Improvement In Survival

ABSTRACTNo effective antiviral therapies are currently available to treat disease after infection with yellow fever virus (YFV). A Syrian golden hamster model of yellow fever (YF) was used to characterize the effect of treatment with BCX4430, a novel adenosine nucleoside analog. Significant improvement in survival was observed after treatment with BCX4430 at 4 mg/kg of body weight per day dosed intraperitoneally (i.p.) twice daily (BID). Treatment with BCX4430 at 12.5 mg/kg/day administered i.p. BID for 7 days offered complete protection from mortality and also resulted in significant improvement of other YF disease parameters, including weight loss, serum alanine aminotransferase levels (6 days postinfection [dpi]), and viremia (4 dpi). In uninfected hamsters, BCX4430 at 200 mg/kg/day administered i.p. BID for 7 days was well tolerated and did not result in mortality or weight loss, suggesting a potentially wide therapeutic index. Treatment with BCX4430 at 12 mg/kg/day i.p. remained effective when administered once daily and for only 4 days. Moreover, BCX4430 dosed at 200 mg/kg/day i.p. BID for 7 days effectively treated YF, even when treatment was delayed up to 4 days after virus challenge, corresponding with peak viral titers in the liver and serum. BCX4430 treatment did not preclude a protective antibody response, as higher neutralizing antibody (nAb) concentrations corresponded with increasing delays of treatment initiation, and greater nAb responses resulted in the protection of animals from a secondary challenge with YFV. In summary, BCX4430 is highly active in a hamster model of YF, even when treatment is initiated at the peak of viral replication.

scholarly journals Golden Syrian hamster as a model to study cardiovascular complications associated with SARS-CoV-2 infection

eLife ◽  
2022 ◽  
Vol 11 ◽  
Author(s):  
Zaigham Abbas Rizvi ◽  
Rajdeep Dalal ◽  
Srikanth Sadhu ◽  
Akshay Binayke ◽  
Jyotsna Dandotiya ◽  
...  
Keyword(s):  
Syrian Hamster ◽  
Troponin I ◽  
Late Phase ◽  
Cardiovascular Complications ◽  
Therapeutic Interventions ◽  
Wall Thickening ◽  
Lung Pathology ◽  
Hamster Model ◽  
Golden Syrian Hamster ◽  
Metabolic Marker

Severe acute respiratory syndrome coronavirus (SARS-CoV)-2 infection in the Golden Syrian hamster causes lung pathology that resembles human coronavirus disease (COVID-19). However, extra-pulmonary pathologies associated with SARS-CoV-2 infection and post COVID sequelae remain to be understood. Here we show, using a hamster model, that the early phase of SARS-CoV-2 infection leads to an acute inflammatory response and lung pathologies, while the late phase of infection causes cardiovascular complications (CVC) characterized by ventricular wall thickening associated with increased ventricular mass/ body mass ratio and interstitial coronary fibrosis. Molecular profiling further substantiated our findings of CVC, as SARS-CoV-2-infected hamsters showed elevated levels of serum cardiac Troponin-I (cTnI), cholesterol, low-density lipoprotein and long-chain fatty acid triglycerides. Serum metabolomics profiling of SARS-CoV-2-infected hamsters identified N-acetylneuraminate, a functional metabolite found to be associated with CVC, as a metabolic marker was found to be common between SARS-CoV-2-infected hamsters and COVID-19 patients. Together, we propose hamsters as a suitable animal model to study post-COVID sequelae associated with CVC which could be extended to therapeutic interventions.

scholarly journals Inactivated rabies virus vectored SARS-CoV-2 vaccine prevents disease in a Syrian hamster model

2021 ◽  
Vol 17 (3) ◽  
pp. e1009383
Author(s):  
Drishya Kurup ◽  
Delphine C. Malherbe ◽  
Christoph Wirblich ◽  
Rachael Lambert ◽  
Adam J. Ronk ◽  
...  
Keyword(s):  
Immune Response ◽  
Weight Loss ◽  
Respiratory Failure ◽  
Syrian Hamster ◽  
Neutralizing Antibodies ◽  
Lung Pathology ◽  
Hamster Model ◽  
Rapid Spread ◽  
Asymptomatic Infections ◽  
Efficacious Vaccine

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is an emergent coronavirus that has caused a worldwide pandemic. Although human disease is often asymptomatic, some develop severe illnesses such as pneumonia, respiratory failure, and death. There is an urgent need for a vaccine to prevent its rapid spread as asymptomatic infections accounting for up to 40% of transmission events. Here we further evaluated an inactivated rabies vectored SARS-CoV-2 S1 vaccine CORAVAX in a Syrian hamster model. CORAVAX adjuvanted with MPLA-AddaVax, a TRL4 agonist, induced high levels of neutralizing antibodies and generated a strong Th1-biased immune response. Vaccinated hamsters were protected from weight loss and viral replication in the lungs and nasal turbinates three days after challenge with SARS-CoV-2. CORAVAX also prevented lung disease, as indicated by the significant reduction in lung pathology. This study highlights CORAVAX as a safe, immunogenic, and efficacious vaccine that warrants further assessment in human trials.

scholarly journals Inactivated rabies virus vectored SARS-CoV-2 vaccine prevents disease in a Syrian hamster model

2021 ◽  
Author(s):  
Drishya Kurup ◽  
Delphine C. Malherbe ◽  
Christoph Wirblich ◽  
Rachael Lambert ◽  
Adam J. Ronk ◽  
...  
Keyword(s):  
Immune Response ◽  
Weight Loss ◽  
Respiratory Failure ◽  
Syrian Hamster ◽  
Neutralizing Antibodies ◽  
Lung Pathology ◽  
Hamster Model ◽  
Rapid Spread ◽  
Asymptomatic Infections ◽  
Efficacious Vaccine

SummarySevere acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is an emergent coronavirus that has caused a worldwide pandemic. Although human disease is often asymptomatic, some develop severe illnesses such as pneumonia, respiratory failure, and death. There is an urgent need for a vaccine to prevent its rapid spread as asymptomatic infections accounting for up to 40% of transmission events. Here we further evaluated an inactivated rabies vectored SARS-CoV-2 S1 vaccine CORAVAX in a Syrian hamster model. CORAVAX adjuvanted with MPLA-AddaVax, a TRL4 agonist, induced high levels of neutralizing antibodies and generated a strong Th1-biased immune response. Vaccinated hamsters were protected from weight loss and viral replication in the lungs and nasal turbinates three days after challenge with SARS-CoV-2. CORAVAX also prevented lung disease, as indicated by the significant reduction in lung pathology. This study highlights CORAVAX as a safe, immunogenic, and efficacious vaccine that warrants further assessment in human trials.

Effect of intestinal alkalinization on irinotecan (CPT-11)-induced diarrhea in the golden Syrian hamster model

2001 ◽  
Vol 120 (5) ◽  
pp. A613-A613
Author(s):  
T IKEGAMI ◽  
P LATHAM ◽  
K KOBAYASHI ◽  
K ARIMORI ◽  
B BOUSCAREL
Keyword(s):  
Syrian Hamster ◽  
Hamster Model ◽  
Golden Syrian Hamster

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 Vasculitis and Neutrophil Extracellular Traps in Lungs of Golden Syrian Hamsters With SARS-CoV-2

2021 ◽  
Vol 12 ◽  
Author(s):  
Kathrin Becker ◽  
Georg Beythien ◽  
Nicole de Buhr ◽  
Stephanie Stanelle-Bertram ◽  
Berfin Tuku ◽  
...  
Keyword(s):  
Animal Models ◽  
Syrian Hamster ◽  
Neutrophil Extracellular Traps ◽  
Virus Antigen ◽  
Endothelial Damage ◽  
Vascular Lesions ◽  
Hamster Model ◽  
Golden Syrian Hamster ◽  
Pulmonary Lesions ◽  
Extracellular Traps

Neutrophil extracellular traps (NETs) have been identified as one pathogenetic trigger in severe COVID-19 cases and therefore well-described animal models to understand the influence of NETs in COVID-19 pathogenesis are needed. SARS-CoV-2 infection causes infection and interstitial pneumonia of varying severity in humans and COVID-19 models. Pulmonary as well as peripheral vascular lesions represent a severe, sometimes fatal, disease complication of unknown pathogenesis in COVID-19 patients. Furthermore, neutrophil extracellular traps (NETs), which are known to contribute to vessel inflammation or endothelial damage, have also been shown as potential driver of COVID-19 in humans. Though most studies in animal models describe the pulmonary lesions characterized by interstitial inflammation, type II pneumocyte hyperplasia, edema, fibrin formation and infiltration of macrophages and neutrophils, detailed pathological description of vascular lesions or NETs in COVID-19 animal models are lacking so far. Here we report different types of pulmonary vascular lesions in the golden Syrian hamster model of COVID-19. Vascular lesions included endothelialitis and vasculitis at 3 and 6 days post infection (dpi), and were almost nearly resolved at 14 dpi. Importantly, virus antigen was present in pulmonary lesions, but lacking in vascular alterations. In good correlation to these data, NETs were detected in the lungs of infected animals at 3 and 6 dpi. Hence, the Syrian hamster seems to represent a useful model to further investigate the role of vascular lesions and NETs in COVID-19 pathogenesis.

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