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tissue distribution of ace2 protein in syrian golden hamster (mesocricetus auratus) and its possible implications in sars-cov-2 related studies.the syrian golden hamster (mesocricetus auratus) has recently been demonstrated as a clinically relevant animal model for sars-cov-2 infection. however, lack of knowledge about the tissue-specific expression pattern of various proteins in these animals and the unavailability of reagents like antibodies against this species hampers these models' optimal use. the major objective of our current study was to analyze the tissue-specific expression pattern of angiotensin-converting enzyme 2, a proven ...202133568991
the g614 pandemic sars-cov-2 variant is not more pathogenic than the original d614 form in adult syrian hamsters.dynamic tracking of variant frequencies among viruses circulating in the global pandemic has revealed the emergence and dominance of a d614g mutation in the sars-cov-2 spike protein. to address whether pandemic sars-cov-2 g614 variant has evolved to become more pathogenic, we infected adult hamsters (>10 months old) with two natural sars-cov-2 variants carrying either d614 or g614 spike protein to mimic infection of the adult/elderly human population. hamsters infected by the two variants exhibi ...202133556653
differential pathogenesis between andes virus strains chi-7913 and chile-9717869in syrian hamsters.hantavirus cardiopulmonary syndrome (hcps) is a severe respiratory disease caused by orthohantaviruses in the americas with a fatality rate as high as 35%. in south america, andes orthohantavirus (hantaviridae, orthohantavirus, andv) is a major cause of hcps, particularly in chile and argentina, where thousands of cases have been reported since the virus was discovered. two strains of andv that are classically used for experimental studies of the virus are chile-9717869, isolated from the natura ...202133627395
n-glycolylneuraminic acid in animal models for human influenza a virus.the first step in influenza virus infection is the binding of hemagglutinin to sialic acid-containing glycans present on the cell surface. over 50 different sialic acid modifications are known, of which n-acetylneuraminic acid (neu5ac) and n-glycolylneuraminic acid (neu5gc) are the two main species. animal models with α2,6 linked neu5ac in the upper respiratory tract, similar to humans, are preferred to enable and mimic infection with unadapted human influenza a viruses. animal models that are c ...202134062844
hamster polyomavirus research: past, present, and future.hamster polyomavirus (mesocricetus auratus polyomavirus 1, hapyv) was discovered as one of the first rodent polyomaviruses at the end of the 1960s in a colony of syrian hamsters (mesocricetus auratus) affected by skin tumors. natural hapyv infections have been recorded in syrian hamster colonies due to the occurrence of skin tumors and lymphomas. hapyv infections of syrian hamsters represent an important and pioneering tumor model. experimental infections of syrian hamsters of different colonies ...202134068409
an immune-competent, replication-permissive syrian hamster glioma model for evaluating delta-24-rgd oncolytic adenovirus.oncolytic adenoviruses are promising new treatments against solid tumors, particularly for glioblastoma (gbm), and preclinical models are required to evaluate the mechanisms of efficacy. however, due to the species selectivity of adenovirus, there is currently no single animal model that supports viral replication, tumor oncolysis, and a virus-mediated immune response. to address this gap, we took advantage of the syrian hamster to develop the first intracranial glioma model that is both adenovi ...202134059921
a systemically deliverable vaccinia virus with increased capacity for intertumoral and intratumoral spread effectively treats pancreatic cancer.pancreatic cancer remains one of the most lethal cancers and is refractory to immunotherapeutic interventions. oncolytic viruses are a promising new treatment option, but current platforms demonstrate limited efficacy, especially for inaccessible and metastatic cancers that require systemically deliverable therapies. we recently described an oncolytic vaccinia virus (vv), vvlδtkδn1l, which has potent antitumor activity, and a regime to enhance intravenous delivery of vv by pharmacological inhibi ...202133500259
coinfection by severe acute respiratory syndrome coronavirus 2 and influenza a(h1n1)pdm09 virus enhances the severity of pneumonia in golden syrian hamsters.clinical outcomes of the interaction between the co-circulating pandemic severe acute respiratory syndrome coronavirus 2 (sars-cov-2) and seasonal influenza viruses are unknown.202133216851
a methyltransferase-defective vsv-based sars-cov-2 vaccine candidate provides complete protection against sars-cov-2 infection in hamsters.the current pandemic of coronavirus disease 2019 (covid-19) caused by severe acute respiratory syndrome coronavirus 2 (sars-cov-2) has led to dramatic economic and health burdens. although the worldwide sars-cov-2 vaccination campaign has begun, exploration of other vaccine candidates is needed due to the uncertainties of the current approved vaccines such as durability of protection, cross-protection against variant strains, and costs of long-term production, and storage. in this study, we deve ...202134379509
development of safe and highly protective live-attenuated sars-cov-2 vaccine candidates by genome recoding.safe and effective vaccines are urgently needed to stop the pandemic caused by severe acute respiratory syndrome coronavirus 2 (sars-cov-2). we construct a series of live attenuated vaccine candidates by large-scale recoding of the sars-cov-2 genome and assess their safety and efficacy in syrian hamsters. animals were vaccinated with a single dose of the respective recoded virus and challenged 21 days later. two of the tested viruses do not cause clinical symptoms but are highly immunogenic and ...202134320400
an enveloped virus-like particle vaccine expressing a stabilized prefusion form of the sars-cov-2 spike protein elicits highly potent immunity.we evaluated enveloped virus-like particles (evlps) expressing various forms of the severe acute respiratory syndrome coronavirus-2 (sars-cov-2) spike protein and several adjuvants in an effort to identify a highly potent coronavirus disease 2019 (covid-19) vaccine candidate. evlps expressing a modified prefusion form of sars-cov-2 spike protein were selected as they induced high antibody binding titers and neutralizing activity after a single injection in mice. formulation of sars-cov-2 s evlps ...202134304928
a single dose of replication-competent vsv-vectored vaccine expressing sars-cov-2 s1 protects against virus replication in a hamster model of severe covid-19.the development of effective countermeasures against severe acute respiratory syndrome coronavirus 2 (sars-cov-2), the agent responsible for the covid-19 pandemic, is a priority. we designed and produced convac, a replication-competent vesicular stomatitis virus (vsv) vaccine vector that expresses the s1 subunit of sars-cov-2 spike protein. we used golden syrian hamsters as animal models of severe covid-19 to test the efficacy of the convac vaccine. a single vaccine dose elicited high levels of ...202134294728
a sars-cov-2 neutralizing antibody selected from covid-19 patients binds to the ace2-rbd interface and is tolerant to most known rbd mutations.the novel betacoronavirus severe acute respiratory syndrome-coronavirus-2 (sars-cov-2) causes a form of severe pneumonia disease called coronavirus disease 2019 (covid-19). to develop human neutralizing anti-sars-cov-2 antibodies, antibody gene libraries from convalescent covid-19 patients were constructed and recombinant antibody fragments (scfv) against the receptor-binding domain (rbd) of the spike protein were selected by phage display. the antibody ste90-c11 shows a subnanometer ic50 in a p ...202134273271
pathogenic and transcriptomic differences of emerging sars-cov-2 variants in the syrian golden hamster model.following the discovery of severe acute respiratory syndrome coronavirus 2 (sars-cov-2) and its rapid spread throughout the world, new viral variants of concern (voc) have emerged. there is a critical need to understand the impact of the emerging variants on host response and disease dynamics to facilitate the development of vaccines and therapeutics. syrian golden hamsters are the leading small animal model that recapitulates key aspects of severe coronavirus disease 2019 (covid-19). in this st ...202134268506
sars-cov-2 infection in the syrian hamster model causes inflammation as well as type i interferon dysregulation in both respiratory and non-respiratory tissues including the heart and kidney.covid-19 (coronavirus disease 2019) caused by sars-cov-2 (severe acute respiratory syndrome coronavirus 2) infection is a disease affecting several organ systems. a model that captures all clinical symptoms of covid-19 as well as long-haulers disease is needed. we investigated the host responses associated with infection in several major organ systems including the respiratory tract, the heart, and the kidneys after sars-cov-2 infection in syrian hamsters. we found significant increases in infla ...202134265022
sex differences in lung imaging and sars-cov-2 antibody responses in a covid-19 golden syrian hamster model.in the coronavirus disease 2019 (covid-19) pandemic caused by the severe acute respiratory syndrome coronavirus 2 (sars-cov-2), more severe outcomes are reported in males than in females, including hospitalizations and deaths. animal models can provide an opportunity to mechanistically interrogate causes of sex differences in the pathogenesis of sars-cov-2. adult male and female golden syrian hamsters (8 to 10 weeks of age) were inoculated intranasally with 105 50% tissue culture infective dose ...202134253053
a single intranasal or intramuscular immunization with chimpanzee adenovirus-vectored sars-cov-2 vaccine protects against pneumonia in hamsters.the development of an effective vaccine against severe acute respiratory syndrome coronavirus 2 (sars-cov-2), the etiologic agent of coronavirus disease 2019 (covid-19), is a global priority. here, we compare the protective capacity of intranasal and intramuscular delivery of a chimpanzee adenovirus-vectored vaccine encoding a prefusion stabilized spike protein (chimpanzee adenovirus [chad]-sars-cov-2-s) in golden syrian hamsters. although immunization with chad-sars-cov-2-s induces robust spike ...202134245672
scalable live-attenuated sars-cov-2 vaccine candidate demonstrates preclinical safety and efficacy.successfully combating the covid-19 pandemic depends on mass vaccination with suitable vaccines to achieve herd immunity. here, we describe covi-vac, the only live attenuated severe acute respiratory syndrome coronavirus 2 (sars-cov-2) vaccine currently in clinical development. covi-vac was developed by recoding a segment of the viral spike protein with synonymous suboptimal codon pairs (codon-pair deoptimization), thereby introducing 283 silent (point) mutations. in addition, the furin cleavage ...202134193524
characterization of a new sars-cov-2 variant that emerged in brazil.the spike (s) protein of severe acute respiratory syndrome coronavirus 2 (sars-cov-2) plays a key role in viral infectivity. it is also the major antigen stimulating the host's protective immune response, specifically, the production of neutralizing antibodies. recently, a new variant of sars-cov-2 possessing multiple mutations in the s protein, designated p.1, emerged in brazil. here, we characterized a p.1 variant isolated in japan by using syrian hamsters, a well-established small animal mode ...202134140350
sars-cov-2 b.1.1.7 infection of syrian hamster does not cause more severe disease, and naturally acquired immunity confers protection.epidemiological studies have revealed the emergence of multiple severe acute respiratory syndrome coronavirus 2 (sars-cov-2) variants of concern (voc), including the lineage b.1.1.7 that is rapidly replacing old variants. the b.1.1.7 variant has been linked to increased morbidity rates, transmissibility, and potentially mortality. to assess viral fitness in vivo and to address whether the b.1.1.7 variant is capable of immune escape, we conducted infection and reinfection studies in naive and con ...202134133199
quantitative proteomics of hamster lung tissues infected with sars-cov-2 reveal host factors having implication in the disease pathogenesis and severity.syrian golden hamsters (mesocricetus auratus) infected by severe acute respiratory syndrome coronavirus 2 (sars-cov-2) manifests lung pathology. in this study, efforts were made to check the infectivity of a local sars-cov-2 isolate in a self-limiting and non-lethal hamster model and evaluate the differential expression of lung proteins during acute infection and convalescence. the findings of this study confirm the infectivity of this isolate in vivo. analysis of clinical parameters and tissue ...202134105201
a qualitative igg elisa for detection of sars-cov-2-specific antibodies in syrian hamster serum samples.this protocol describes an indirect enzyme-linked immunosorbent assay for qualitative detection of igg antibodies against severe acute respiratory syndrome coronavirus 2 (sars-cov-2) in syrian hamster serum samples. we describe the preparation of inactivated virus antigens and the negative control antigen and the use of antigen-coated microtiter plates to detect sars-cov-2-specific antibodies from sars-cov-2-infected hamsters, including the criteria for differentiating positive versus negative r ...202133997801
nucleocapsid vaccine elicits spike-independent sars-cov-2 protective immunity.severe acute respiratory syndrome coronavirus 2 (sars-cov-2) is responsible for the covid-19 pandemic. neutralizing antibodies target the receptor binding domain of the spike (s) protein, a focus of successful vaccine efforts. concerns have arisen that s-specific vaccine immunity may fail to neutralize emerging variants. we show that vaccination with had5 expressing the nucleocapsid (n) protein can establish protective immunity, defined by reduced weight loss and viral load, in both syrian hamst ...202133948591
covid-19-related anosmia is associated with viral persistence and inflammation in human olfactory epithelium and brain infection in hamsters.whereas recent investigations have revealed viral, inflammatory, and vascular factors involved in severe acute respiratory syndrome coronavirus 2 (sars-cov-2) lung pathogenesis, the pathophysiology of neurological disorders in coronavirus disease 2019 (covid-19) remains poorly understood. olfactory and taste dysfunction are common in covid-19, especially in mildly symptomatic patients. here, we conducted a virologic, molecular, and cellular study of the olfactory neuroepithelium of seven patient ...202133941622
vascular inflammation is associated with loss of aquaporin 1 expression on endothelial cells and increased fluid leakage in sars-cov-2 infected golden syrian hamsters.vascular changes represent a characteristic feature of severe acute respiratory syndrome coronavirus-2 (sars-cov-2) infection leading to a breakdown of the vascular barrier and subsequent edema formation. the aim of this study was to provide a detailed characterization of the vascular alterations during sars-cov-2 infection and to evaluate the impaired vascular integrity. groups of ten golden syrian hamsters were infected intranasally with sars-cov-2 or phosphate-buffered saline (mock infection) ...202133918079
sex differences in lung imaging and sars-cov-2 antibody responses in a covid-19 golden syrian hamster model.in the ongoing coronavirus disease 2019 (covid-19) pandemic caused by the severe acute respiratory syndrome coronavirus 2 (sars-cov-2), more severe outcomes are reported in males compared with females, including hospitalizations and deaths. animal models can provide an opportunity to mechanistically interrogate causes of sex differences in the pathogenesis of sars-cov-2. adult male and female golden syrian hamsters (8-10 weeks of age) were inoculated intranasally with 10 5 tcid 50 of sars-cov-2/ ...202133821269
inactivated rabies virus vectored sars-cov-2 vaccine prevents disease in a syrian hamster model.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 hamste ...202133765062
a safe and highly efficacious measles virus-based vaccine expressing sars-cov-2 stabilized prefusion spike.the current pandemic of covid-19 caused by severe acute respiratory syndrome coronavirus 2 (sars-cov-2) highlights an urgent need to develop a safe, efficacious, and durable vaccine. using a measles virus (rmev) vaccine strain as the backbone, we developed a series of recombinant attenuated vaccine candidates expressing various forms of the sars-cov-2 spike (s) protein and its receptor binding domain (rbd) and evaluated their efficacy in cotton rat, ifnar-/-mice, ifnar-/--hcd46 mice, and golden ...202133688034
robust sars-cov-2 infection in nasal turbinates after treatment with systemic neutralizing antibodies.severe acute respiratory syndrome coronavirus 2 (sars-cov-2) is characterized by a burst in the upper respiratory portal for high transmissibility. to determine human neutralizing antibodies (hunabs) for entry protection, we tested three potent hunabs (ic50 range, 0.0007-0.35 μg/ml) against live sars-cov-2 infection in the golden syrian hamster model. these hunabs inhibit sars-cov-2 infection by competing with human angiotensin converting enzyme-2 for binding to the viral receptor binding domain ...202133657424
regeneration profiles of olfactory epithelium after sars-cov-2 infection in golden syrian hamsters.olfactory dysfunction is one of the most frequent and specific symptoms of coronavirus disease 2019 (covid-19). information on the damage and repair of the neuroepithelium and its impact on olfactory function after covid-19 is still incomplete. while severe acute respiratory syndrome coronavirus-2 (sars-cov-2) causes the ongoing worldwide outbreak of covid-19, little is known about the changes triggered by sars-cov-2 in the olfactory epithelium (oe) at the cellular level. here, we report profile ...202133522795
immunogenicity and protective efficacy of bbv152, whole virion inactivated sars- cov-2 vaccine candidates in the syrian hamster model.the availability of a safe and effective vaccine would be the eventual measure to deal with severe acute respiratory syndrome coronavirus-2 (sars-cov-2) threat. here, we have assessed the immunogenicity and protective efficacy of inactivated sars-cov-2 vaccine candidates bbv152a, bbv152b, and bbv152c in syrian hamsters. three dose vaccination regimes with vaccine candidates induced significant titers of sars-cov-2-specific igg and neutralizing antibodies. bbv152a and bbv152b vaccine candidates r ...202133521604
absence of vaccine-enhanced disease with unexpected positive protection against severe acute respiratory syndrome coronavirus 2 (sars-cov-2) by inactivated vaccine given within 3 days of virus challenge in syrian hamster model.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.202133515458
sars-cov-2 causes a systemically multiple organs damages and dissemination in hamsters.severe acute respiratory syndrome coronavirus-2 (sars-cov-2) has spread across the world and impacted global healthcare systems. for clinical patients, covid-19 not only induces pulmonary lesions but also affects extrapulmonary organs. an ideal animal model that mimics covid-19 in humans in terms of the induced systematic lesions is urgently needed. here, we report that syrian hamster is highly permissive to sars-cov-2 and exhibit diffuse alveolar damage and induced extrapulmonary multi-organs d ...202133510731
ace2-variants indicate potential sars-cov-2-susceptibility in animals: a molecular dynamics study.severe acute respiratory syndrome coronavirus 2 (sars-cov-2) continues to be a global threat, causing millions of deaths worldwide. sars-cov-2 is an enveloped virus with spike (s) glycoproteins conferring binding to the host cell's angiotensin-converting enzyme 2 (ace2), which is critical for cellular entry. the host range of the virus extends well beyond humans and non-human primates. natural and experimental infections have confirmed the high susceptibility of cats, ferrets, and syrian hamster ...202134378348
animal models of covid-19 ii. comparative immunology.developing strong animal models is essential for furthering our understanding of how the immune system functions in response to severe acute respiratory syndrome coronavirus 2 (sars-cov-2) infection. the alarming speed at which sars-cov-2 has spread, and the high mortality rate of severe coronavirus disease 2019 (covid-19), has required both basic science and clinical research to move at an unprecedented pace. models previously developed to study the immune response against sars-cov have been ra ...202133914873
preclinical development of a molecular clamp-stabilised subunit vaccine for severe acute respiratory syndrome coronavirus 2.efforts to develop and deploy effective vaccines against severe acute respiratory syndrome coronavirus 2 (sars-cov-2) continue at pace. here, we describe rational antigen design through to manufacturability and vaccine efficacy of a prefusion-stabilised spike (s) protein, sclamp, in combination with the licensed adjuvant mf59 'mf59c.1' (seqirus, parkville, australia).202133841880
sars-cov-2 in animals: potential for unknown reservoir hosts and public health implications.severe acute respiratory syndrome coronavirus 2 (sars-cov-2, previously 2019-ncov) is suspected of having originated in 2019 in china from a coronavirus infected bat of the genus rhinolophus. following the initial emergence, possibly facilitated by a mammalian bridge host, sars-cov-2 is currently transmitted across the globe via efficient human-to-human transmission. results obtained from experimental studies indicate that animal species such as cats, ferrets, raccoon dogs, cynomolgus macaques, ...202133892621
cova1-18 neutralizing antibody protects against sars-cov-2 in three preclinical models.one year into the coronavirus disease 2019 (covid-19) pandemic caused by severe acute respiratory syndrome coronavirus 2 (sars-cov-2), effective treatments are still needed 1-3 . monoclonal antibodies, given alone or as part of a therapeutic cocktail, have shown promising results in patients, raising the hope that they could play an important role in preventing clinical deterioration in severely ill or in exposed, high risk individuals 4-6 . here, we evaluated the prophylactic and therapeutic ef ...202133619476
ad26.cov2.s protects syrian hamsters against g614 spike variant sars-cov-2 and does not enhance respiratory disease.previously we have shown that a single dose of recombinant adenovirus serotype 26 (ad26) vaccine expressing a prefusion stabilized sars-cov-2 spike antigen (ad26.cov2.s) is immunogenic and provides protection in syrian hamster and non-human primate sars-cov-2 infection models. here, we investigated the immunogenicity, protective efficacy, and potential for vaccine-associated enhanced respiratory disease (vaerd) mediated by ad26.cov2.s in a moderate disease syrian hamster challenge model, using t ...202133741993
nucleocapsid vaccine elicits spike-independent sars-cov-2 protective immunity.severe acute respiratory syndrome coronavirus 2 (sars-cov-2) is responsible for the covid-19 pandemic. neutralizing abs target the receptor binding domain of the spike (s) protein, a focus of successful vaccine efforts. concerns have arisen that s-specific vaccine immunity may fail to neutralize emerging variants. we show that vaccination with a human adenovirus type 5 vector expressing the sars-cov-2 nucleocapsid (n) protein can establish protective immunity, defined by reduced weight loss and ...202134193597
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