Inhibition of Severe Acute Respiratory Syndrome-Associated Coronavirus Infection by Equine Neutralizing Antibody in Golden Syrian Hamsters

2007 ◽  
Vol 20 (1) ◽  
pp. 197-205 ◽  
Author(s):  
Guangyu Zhao ◽  
Bing Ni ◽  
Haiyan Jiang ◽  
Deyan Luo ◽  
Marek Pacal ◽  
...  
Keyword(s):  
Severe Acute Respiratory Syndrome ◽  
Neutralizing Antibody ◽  
Syrian Hamsters ◽  
Coronavirus Infection

scholarly journals Severe Acute Respiratory Syndrome Coronavirus Infection of Golden Syrian Hamsters

2005 ◽  
Vol 79 (1) ◽  
pp. 503-511 ◽  
Author(s):  
Anjeanette Roberts ◽  
Leatrice Vogel ◽  
Jeannette Guarner ◽  
Norman Hayes ◽  
Brian Murphy ◽  
...  
Keyword(s):  
Severe Acute Respiratory Syndrome ◽  
Respiratory Tract ◽  
Virus Replication ◽  
Neutralizing Antibodies ◽  
Antiviral Agents ◽  
Small Animal ◽  
Pulmonary Tissue ◽  
Syrian Hamsters ◽  
Significant Pathology ◽  
Coronavirus Infection

ABSTRACT Small animal models are needed in order to evaluate the efficacy of candidate vaccines and antivirals directed against the severe acute respiratory syndrome coronavirus (SARS CoV). We investigated the ability of SARS CoV to infect 5-week-old Golden Syrian hamsters. When administered intranasally, SARS CoV replicates to high titers in the lungs and nasal turbinates. Peak replication in the lower respiratory tract was noted on day 2 postinfection (p.i.) and was cleared by day 7 p.i. Low levels of virus were present in the nasal turbinates of a few hamsters at 14 days p.i. Viral replication in epithelial cells of the respiratory tract was accompanied by cellular necrosis early in infection, followed by an inflammatory response coincident with viral clearance, focal consolidation in pulmonary tissue, and eventual pulmonary tissue repair. Despite high levels of virus replication and associated pathology in the respiratory tract, the hamsters showed no evidence of disease. Neutralizing antibodies were detected in sera at day 7 p.i., and mean titers at day 28 p.i. exceeded 1:400. Hamsters challenged with SARS CoV at day 28 p.i. were completely protected from virus replication and accompanying pathology in the respiratory tract. Comparing these data to the mouse model, SARS CoV replicates to a higher titer and for a longer duration in the respiratory tract of hamsters and is accompanied by significant pathology that is absent in mice. Viremia and extrapulmonary spread of SARS CoV to liver and spleen, which are seen in hamsters, were not detected in mice. The hamster, therefore, is superior to the mouse as a model for the evaluation of antiviral agents and candidate vaccines against SARS CoV replication.

scholarly journals SARS-CoV-2 hijacks neutralizing dimeric IgA for enhanced nasal infection and injury

2021 ◽  
Author(s):  
Biao Zhou ◽  
Runhong Zhou ◽  
Jasper Fuk-Woo Chan ◽  
Jianwei Zeng ◽  
Qi Zhang ◽  
...  
Keyword(s):  
Severe Acute Respiratory Syndrome ◽  
Angiotensin Converting Enzyme ◽  
Neutralizing Antibody ◽  
Receptor Binding Domain ◽  
Converting Enzyme ◽  
Angiotensin Converting Enzyme 2 ◽  
Nasal Turbinate ◽  
Syrian Hamsters ◽  
Iga Antibodies ◽  
Potent Neutralization

Robust severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) infection in nasal turbinate (NT) accounts for high viral transmissibility, yet whether neutralizing IgA antibodies can control it remains unknown. Here, we evaluated receptor binding domain (RBD)-specific monomeric B8-mIgA1 and B8-mIgA2, and dimeric B8-dIgA1 and B8-dIgA2 against intranasal SARS-CoV-2 challenge in Syrian hamsters. These antibodies exhibited comparably potent neutralization against authentic virus by competing with human angiotensin converting enzyme-2 (ACE2) receptor for RBD binding. While reducing viruses in lungs, pre-exposure intranasal B8-dIgA1 or B8-dIgA2 led to 81-fold more infectious viruses and severer damage in NT than placebo. Virus-bound B8-dIgA1 and B8-dIgA2 could engage CD209 as an alternative receptor for entry into ACE2-negative cells and allowed viral cell-to-cell transmission. Cryo-EM revealed B8 as a class II neutralizing antibody binding trimeric RBDs in 3-up or 2-up/1-down conformation. Therefore, RBD-specific neutralizing dIgA engages an unexpected action for enhanced SARS-CoV-2 nasal infection and injury in Syrian hamsters.

scholarly journals SARS-CoV-2 hijacks neutralizing dimeric IgA for enhanced nasal infection and injury

2021 ◽  
Author(s):  
Biao Zhou ◽  
Runhong Zhou ◽  
Jasper Fuk-Woo Chan ◽  
Jianwei Zeng ◽  
Qi Zhang ◽  
...  
Keyword(s):  
Severe Acute Respiratory Syndrome ◽  
Angiotensin Converting Enzyme ◽  
Neutralizing Antibody ◽  
Receptor Binding Domain ◽  
Converting Enzyme ◽  
Angiotensin Converting Enzyme 2 ◽  
Nasal Turbinate ◽  
Syrian Hamsters ◽  
Iga Antibodies ◽  
Potent Neutralization

Abstract Robust severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) infection in nasal turbinate (NT) accounts for high viral transmissibility, yet whether neutralizing IgA antibodies can control it remains unknown. Here, we evaluated receptor binding domain (RBD)-specific monomeric B8-mIgA1 and B8-mIgA2, and dimeric B8-dIgA1 and B8-dIgA2 against intranasal SARS-CoV-2 challenge in Syrian hamsters. These antibodies exhibited comparably potent neutralization against authentic virus by competing with human angiotensin converting enzyme-2 (ACE2) receptor for RBD binding. While reducing viruses in lungs, pre-exposure intranasal B8-dIgA1 or B8-dIgA2 led to 81-fold more infectious viruses and severer damage in NT than placebo. Virus-bound B8-dIgA1 and B8-dIgA2 could engage CD209 as an alternative receptor for entry into ACE2-negative cells and allowed viral cell-to-cell transmission. Cryo-EM revealed B8 as a class II neutralizing antibody binding trimeric RBDs in 3-up or 2-up/1-down conformation. Therefore, RBD-specific neutralizing dIgA engages an unexpected action for enhanced SARS-CoV-2 nasal infection and injury in Syrian hamsters.

scholarly journals Delayed neutralizing antibody response in the acute phase correlates with severe progression of COVID-19

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Hitoshi Kawasuji ◽  
Yoshitomo Morinaga ◽  
Hideki Tani ◽  
Miyuki Kimura ◽  
Hiroshi Yamada ◽  
...  
Keyword(s):  
Severe Acute Respiratory Syndrome ◽  
Neutralization Test ◽  
Neutralizing Antibody ◽  
Pseudotyped Virus ◽  
Serum Samples ◽  
Neutralization Activity ◽  
Neutralizing Activity ◽  
Time Points ◽  
Moderate Disease ◽  
Activity Dynamics

AbstractAdaptive immunity to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) dynamics remain largely unknown. The neutralizing antibody (NAb) levels in patients with coronavirus disease 2019 (COVID-19) are helpful for understanding the pathology. Using SARS-CoV-2 pseudotyped virus, serum sample neutralization values in symptomatic COVID-19 patients were measured using the chemiluminescence reduction neutralization test (CRNT). At least two sequential serum samples collected during hospitalization were analyzed to assess NAbs neutralizing activity dynamics at different time points. Of the 11 patients, four (36.4%), six (54.5%), and one (9.1%) had moderate, severe, and critical disease, respectively. Fifty percent neutralization (N50%-CRNT) was observed upon admission in 90.9% (10/11); all patients acquired neutralizing activity 2–12 days after onset. In patients with moderate disease, neutralization was observed at earliest within two days after symptom onset. In patients with severe-to-critical disease, neutralization activity increased, plateauing 9–16 days after onset. Neutralization activity on admission was significantly higher in patients with moderate disease than in patients with severe-to-critical disease (relative % of infectivity, 6.4% vs. 41.1%; P = .011). Neutralization activity on admission inversely correlated with disease severity. The rapid NAb response may play a crucial role in preventing the progression of COVID-19.

scholarly journals Multivalent nanoparticle-based vaccines protect hamsters against SARS-CoV-2 after a single immunization

2021 ◽  
Vol 4 (1) ◽  
Author(s):  
Shiho Chiba ◽  
Steven J. Frey ◽  
Peter J. Halfmann ◽  
Makoto Kuroda ◽  
Tadashi Maemura ◽  
...  
Keyword(s):  
Coat Protein ◽  
Infectious Virus ◽  
Neutralizing Antibody ◽  
Vaccine Platform ◽  
Death Rates ◽  
Widespread Distribution ◽  
Syrian Hamsters ◽  
Vaccine Trials ◽  
Multiple Copies ◽  
Antibody Titers

AbstractThe COVID-19 pandemic continues to wreak havoc as worldwide SARS-CoV-2 infection, hospitalization, and death rates climb unabated. Effective vaccines remain the most promising approach to counter SARS-CoV-2. Yet, while promising results are emerging from COVID-19 vaccine trials, the need for multiple doses and the challenges associated with the widespread distribution and administration of vaccines remain concerns. Here, we engineered the coat protein of the MS2 bacteriophage and generated nanoparticles displaying multiple copies of the SARS-CoV-2 spike (S) protein. The use of these nanoparticles as vaccines generated high neutralizing antibody titers and protected Syrian hamsters from a challenge with SARS-CoV-2 after a single immunization with no infectious virus detected in the lungs. This nanoparticle-based vaccine platform thus provides protection after a single immunization and may be broadly applicable for protecting against SARS-CoV-2 and future pathogens with pandemic potential.

scholarly journals A single immunization with a rhabdovirus-based vector expressing severe acute respiratory syndrome coronavirus (SARS-CoV) S protein results in the production of high levels of SARS-CoV-neutralizing antibodies

2005 ◽  
Vol 86 (5) ◽  
pp. 1435-1440 ◽  
Author(s):  
Milosz Faber ◽  
Elaine W. Lamirande ◽  
Anjeanette Roberts ◽  
Amy B. Rice ◽  
Hilary Koprowski ◽  
...  
Keyword(s):  
Severe Acute Respiratory Syndrome ◽  
Neutralizing Antibodies ◽  
Neutralizing Antibody ◽  
Protein S ◽  
S Protein ◽  
Cellular Immune Responses ◽  
Glycoprotein G ◽  
Cellular Immune ◽  
Animal Reservoirs ◽  
S Genes

Foreign viral proteins expressed by rabies virus (RV) have been shown to induce potent humoral and cellular immune responses in immunized animals. In addition, highly attenuated and, therefore, very safe RV-based vectors have been constructed. Here, an RV-based vaccine vehicle was utilized as a novel vaccine against severe acute respiratory syndrome coronavirus (SARS-CoV). For this approach, the SARS-CoV nucleocapsid protein (N) or envelope spike protein (S) genes were cloned between the RV glycoprotein G and polymerase L genes. Recombinant vectors expressing SARS-CoV N or S protein were recovered and their immunogenicity was studied in mice. A single inoculation with the RV-based vaccine expressing SARS-CoV S protein induced a strong SARS-CoV-neutralizing antibody response. The ability of the RV-SARS-CoV S vector to confer immunity after a single inoculation makes this live vaccine a promising candidate for eradication of SARS-CoV in animal reservoirs, thereby reducing the risk of transmitting the infection to humans.

scholarly journals Asymptomatic Severe Acute Respiratory Syndrome–associated Coronavirus Infection

2003 ◽  
Vol 9 (11) ◽  
pp. 1491-1492 ◽  
Author(s):  
Harold K.K. Lee ◽  
Eugene Y.K. Tso ◽  
T. N. Chau ◽  
Owen T.Y. Tsang ◽  
W. Choi ◽  
...  
Keyword(s):  
Severe Acute Respiratory Syndrome ◽  
Coronavirus Infection

scholarly journals An Update on Animal Models for Severe Acute Respiratory Syndrome Coronavirus 2 Infection and Countermeasure Development

2021 ◽  
Vol 12 ◽  
Author(s):  
Liang Zhang ◽  
Shuaiyin Chen ◽  
Weiguo Zhang ◽  
Haiyan Yang ◽  
Yuefei Jin ◽  
...  
Keyword(s):  
Animal Models ◽  
Severe Acute Respiratory Syndrome ◽  
Research Progress ◽  
Laboratory Mice ◽  
Disease Manifestation ◽  
Highly Pathogenic ◽  
The World ◽  
Coronavirus Infection ◽  
Different Levels ◽  
Critical Aspects

Coronavirus Disease 2019 (COVID-19) caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has become a pandemic since March 2020 and led to significant challenges to over 200 countries and regions all over the world. The establishment of highly pathogenic coronavirus animal model is beneficial for the study of vaccines and pathogenic mechanism of the virus. Laboratory mice, Syrian hamsters, Non-human primates and Ferrets have been used to establish animal models of emerging coronavirus infection. Different animal models can reproduce clinical infection symptoms at different levels. Appropriate animal models are of great significance for the pathogenesis of COVID-19 and the research progress related to vaccines. This review aims to introduce the current progress about experimental animal models for SARS-CoV-2, and collectively generalize critical aspects of disease manifestation in humans and increase their usefulness in research into COVID-19 pathogenesis and developing new preventions and treatments.

scholarly journals A case of severe acute respiratory syndrome coronavirus 2 with acute thrombotic cerebral infarction and generalized thrombosis

2021 ◽  
pp. 405-408
Author(s):  
Sylvia Nikolaeva Genova ◽  
Nikolaeva Genova ◽  
Mina Miroslavova Pencheva ◽  
Alexander Georgiev Ivanov
Keyword(s):  
Severe Acute Respiratory Syndrome ◽  
Cerebral Infarction ◽  
Viral Pneumonia ◽  
Autopsy Case ◽  
Full Spectrum ◽  
Histological Changes ◽  
Large Size ◽  
Thrombotic Complications ◽  
Coronavirus Infection ◽  
The Brain

The full spectrum of coronavirus disease 2019 (COVID-19) has not been fully described yet. COVID-19 is associated with a high risk of thrombotic complications such as venous thromboembolism and cerebrovascular disease. Here, we report an autopsy case of a 55-year-old woman diagnosed with severe viral pneumonia complicated by acute cerebral infarction and venous and arterial thrombosis in different organs. The patient died due to severe acute respiratory syndrome coronavirus 2. Macroscopically and histologically, in addition to viral pneumonia and diffuse hemorrhages, fibrin clots were found in arteries and venous vessels of medium and large size in the brain, lungs, and pancreas. Propagation of cerebrovascular thrombosis has led to extensive cerebral infarction. The dating of this infarction, according to the macroscopical findings and the histological changes, was between 24 and 48 h before death. This case confirms the hypothesis on the risk of generalized arterial and venous thromboses in coronavirus infection.

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