scholarly journals Protective immunity of the primary SARS-CoV-2 infection reduces disease severity post re-infection with Delta variants in Syrian hamsters

2021 ◽  
Author(s):  
Sreelekshmy Mohandas ◽  
Pragya Yadav ◽  
Anita Shete ◽  
Dimpal Nyayanit ◽  
Rajlaxmi Jain ◽  
...  
Keyword(s):  
Viral Load ◽  
Protective Immunity ◽  
Herd Immunity ◽  
Neutralizing Antibody ◽  
Lung Pathology ◽  
Upper Respiratory Tract ◽  
Weight Changes ◽  
Syrian Hamsters ◽  
Viral Shedding ◽  
Prolonged Duration

Delta variant has evolved to become dominant SARS-CoV-2 lineage worldwide and there are reports of secondary infections with varying severity in vaccinated and unvaccinated naturally recovered COVID-19 patients. As the protective immunity following the infection wanes within few months, studies of re-infection after prolonged duration is needed. Hence we assessed the potential of re-infection by Delta, Delta AY.1 and B.1 in COVID-19 recovered hamsters after 3 months of infection. Re-infection with Delta and B.1 variants in hamsters showed reduced viral shedding, lung pathology and lung viral load, whereas the upper respiratory tract viral load remained similar to that of first infection. The reduction in viral load and lung pathology after re-infection with Delta AY.1 variant was not marked. Further we assessed the disease characteristics of Delta AY.1 to understand whether it has any replication advantage over Delta variant and B.1 variant, an early isolate in Syrian hamsters. Body weight changes, viral load in respiratory organs, lung pathology, cytokine response and neutralizing antibody response were assessed. Delta AY.1 variant produced milder disease in comparison to Delta variant and the neutralizing response was similar against Delta, B.1 and B.1.351 variant in contrast to Delta or B.1 infected hamsters which showed a significant reduction in neutralization titres against B.1.351. Elevation of IL-6 levels was observed post infection in hamsters after primary infection. The prior infection could not produce sterilizing immunity but the protective effect was evident following re-infection. This indicates the importance of the transmission prevention efforts even after achieving herd immunity.

scholarly journals Dose-dependent response to infection with SARS-CoV-2 in the ferret model and evidence of protective immunity

2021 ◽  
Vol 12 (1) ◽  
Author(s):  
Kathryn A. Ryan ◽  
Kevin R. Bewley ◽  
Susan A. Fotheringham ◽  
Gillian S. Slack ◽  
Phillip Brown ◽  
...  
Keyword(s):  
Protective Immunity ◽  
Viral Rna ◽  
Dose Titration ◽  
High Dose ◽  
Lung Pathology ◽  
Upper Respiratory Tract ◽  
Virus Shedding ◽  
Upper Respiratory ◽  
Dose Dependent ◽  
Titration Study

AbstractThere is a vital need for authentic COVID-19 animal models to enable the pre-clinical evaluation of candidate vaccines and therapeutics. Here we report a dose titration study of SARS-CoV-2 in the ferret model. After a high (5 × 106 pfu) and medium (5 × 104 pfu) dose of virus is delivered, intranasally, viral RNA shedding in the upper respiratory tract (URT) is observed in 6/6 animals, however, only 1/6 ferrets show similar signs after low dose (5 × 102 pfu) challenge. Following sequential culls pathological signs of mild multifocal bronchopneumonia in approximately 5–15% of the lung is seen on day 3, in high and medium dosed groups. Ferrets re-challenged, after virus shedding ceased, are fully protected from acute lung pathology. The endpoints of URT viral RNA replication & distinct lung pathology are observed most consistently in the high dose group. This ferret model of SARS-CoV-2 infection presents a mild clinical disease.

scholarly journals Effect of prophylactic use of intra-nasal oil formulations in the hamster model of Covid-19

2021 ◽  
Author(s):  
Zaigham Abbas Rizvi ◽  
Manas Ranjan Tripathy ◽  
Nishant Sharma ◽  
Sandeep Goswami ◽  
N Srikanth ◽  
...  
Keyword(s):  
Viral Load ◽  
Respiratory Tract ◽  
Viral Entry ◽  
Body Weight Loss ◽  
Lung Pathology ◽  
Upper Respiratory Tract ◽  
Hamster Model ◽  
Reduced Body ◽  
Upper Respiratory ◽  
Prophylactic Use

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV2) infection initiates with viral entry in upper respiratory tract leading to coronavirus disease 2019 (Covid-19). Severe Covid-19 is characterized by pulmonary pathologies associated with respiratory failure. Thus, therapeutics aimed at inhibiting entry of the virus or its internalization in the upper respiratory tract, are of interest. Herein, we report the prophylactic application of two intra-nasal formulations provided by the National Medicinal Plant Board (NMPB), Anu oil and Til tailya in SARS-CoV2 infection hamster model. Prophylactic nasal instillation of these oil formulations exhibited reduced viral load in lungs, and resulted in reduced body weight loss and pneumonitis. In line with reduced viral load, histopathlogical analysis revealed a reduction in lung pathology in Anu oil group as compared to the control infected group. However, Til tailya group did not show a significant reduction in lung pathology. Furthermore, molecular analysis using mRNA expression profiling indicated reduced expression of pro-inflammatory cytokines genes, including Th1 and Th17 cytokines for both the intra-nasal formulations as a result of decreased viral load. Together, the prophylactic intra-nasal application of Annu oil seems to be useful in limiting both the viral load and disease severity disease in SARS-CoV2 infection in hamster model.

scholarly journals Establishment of a pig influenza challenge model for evaluation of monoclonal antibody delivery platforms

2020 ◽  
Author(s):  
Adam McNee ◽  
Trevor Smith ◽  
Barbara Holzer ◽  
Becky Clark ◽  
Emily Bessell ◽  
...  
Keyword(s):  
Monoclonal Antibody ◽  
Monoclonal Antibodies ◽  
Viral Load ◽  
Influenza Virus Infection ◽  
Small Animal ◽  
H1n1 Influenza ◽  
Lung Pathology ◽  
Host Animal ◽  
Viral Shedding ◽  
Robust Model

AbstractMonoclonal antibodies are a possible adjunct to vaccination and drugs in treatment of influenza virus infection. However questions remain whether small animal models accurately predict efficacy in humans. We have established the pig, a large natural host animal for influenza, with many physiological similarities to humans, as a robust model for testing monoclonal antibodies. We show that a strongly neutralizing monoclonal antibody (2-12C) against the hemagglutinin head administered prophylactically at 15 mg/kg reduced viral load and lung pathology after pandemic H1N1 influenza challenge. A lower dose of 1 mg/kg of 2-12C or a DNA plasmid encoded version of 2-12C, reduced pathology and viral load in the lungs, but not viral shedding in nasal swabs. We propose that the pig influenza model will be useful for testing candidate monoclonal antibodies and emerging delivery platforms prior to human trials.

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 Ad26.COV2.S-elicited immunity protects against G614 spike variant SARS-CoV-2 infection in Syrian hamsters and does not enhance respiratory disease in challenged animals with breakthrough infection after sub-optimal vaccine dosing

2021 ◽  
Author(s):  
Joan E.M. van der Lubbe ◽  
Sietske K. Rosendahl Huber ◽  
Aneesh Vijayan ◽  
Liesbeth Dekking ◽  
Ella van Huizen ◽  
...  
Keyword(s):  
Respiratory Tract ◽  
Respiratory Disease ◽  
Syrian Hamster ◽  
Vaccine Dose ◽  
Neutralizing Antibody ◽  
Upper Respiratory Tract ◽  
Breakthrough Infection ◽  
Syrian Hamsters ◽  
Antibody Titers ◽  
Upper Respiratory

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 the currently most prevalent G614 spike SARS-CoV-2 variant. Vaccine doses of 1x109 vp and 1x1010 vp elicited substantial neutralizing antibodies titers and completely protected over 80% of SARS-CoV-2 inoculated Syrian hamsters from lung infection and pneumonia but not upper respiratory tract infection. A second vaccine dose further increased neutralizing antibody titers which was associated with decreased infectious viral load in the upper respiratory tract after SARS-CoV-2 challenge. Suboptimal non-protective immune responses elicited by low-dose A26.COV2.S vaccination did not exacerbate respiratory disease in SARS-CoV-2-inoculated Syrian hamsters with breakthrough infection. In addition, dosing down the vaccine allowed to establish that binding and neutralizing antibody titers correlate with lower respiratory tract protection probability. Overall, these pre-clinical data confirm efficacy of a 1-dose vaccine regimen with Ad26.COV2.S in this G614 spike SARS-CoV-2 virus variant Syrian hamster model, show the added benefit of a second vaccine dose, and demonstrate that there are no signs of VAERD under conditions of suboptimal immunity.

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 Early-Morning vs Spot Posterior Oropharyngeal Saliva for Diagnosis of SARS-CoV-2 Infection: Implication of Timing of Specimen Collection for Community-Wide Screening

2020 ◽  
Vol 7 (6) ◽  
Author(s):  
Derek Ling-Lung Hung ◽  
Xin Li ◽  
Kelvin Hei-Yeung Chiu ◽  
Cyril Chik-Yan Yip ◽  
Kelvin Kai-Wang To ◽  
...  
Keyword(s):  
Viral Load ◽  
Diagnostic Yield ◽  
Statistical Significance ◽  
Early Morning ◽  
Optimal Timing ◽  
Molecular Testing ◽  
Upper Respiratory Tract ◽  
Community Screening ◽  
Time Points ◽  
Viral Shedding

Abstract Background Posterior oropharyngeal saliva is increasingly recognized as a valid respiratory specimen for SARS-CoV-2 diagnosis. It is easy to collect and suitable for community-wide screening. The optimal timing of collection is currently unknown, and we speculate that an early-morning specimen before oral hygiene and breakfast would increase the diagnostic yield. Methods Posterior oropharyngeal saliva was collected at 5 different time points within the same day from 18 patients with previously confirmed SARS-CoV-2 infection by molecular testing. Cycle threshold (Ct) values were compared. Results There was an overall trend of lower Ct values from specimens collected in the early morning, with a gradual decrease of viral load towards nighttime, but reaching statistical significance only when compared with the specimens collected at bedtime. Eight out of 13 subjects had a higher viral load in the early morning than the rest of the 4 time points (before lunch, before teatime at 3 pm, before dinner, before bedtime). Conclusions The result suggests a diurnal variation of viral shedding from the upper respiratory tract with a trend showing higher viral load in the early morning. For community screening purposes, posterior oropharyngeal saliva could be taken throughout the day, but preferably in the early morning to maximize the yield.

scholarly journals Ad26.COV2.S protects Syrian hamsters against G614 spike variant SARS-CoV-2 and does not enhance respiratory disease

npj Vaccines ◽  
2021 ◽  
Vol 6 (1) ◽  
Author(s):  
Joan E. M. van der Lubbe ◽  
Sietske K. Rosendahl Huber ◽  
Aneesh Vijayan ◽  
Liesbeth Dekking ◽  
Ella van Huizen ◽  
...  
Keyword(s):  
Respiratory Tract ◽  
Respiratory Disease ◽  
Syrian Hamster ◽  
Neutralizing Antibodies ◽  
Vaccine Dose ◽  
Neutralizing Antibody ◽  
Upper Respiratory Tract ◽  
Syrian Hamsters ◽  
Antibody Titers ◽  
Upper Respiratory

AbstractPreviously 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 the currently most prevalent G614 spike SARS-CoV-2 variant. Vaccine doses of 1 × 109 and 1 × 1010 VP elicited substantial neutralizing antibodies titers and completely protected over 80% of SARS-CoV-2 inoculated Syrian hamsters from lung infection and pneumonia but not upper respiratory tract infection. A second vaccine dose further increased neutralizing antibody titers that was associated with decreased infectious viral load in the upper respiratory tract after SARS-CoV-2 challenge. Suboptimal non-protective immune responses elicited by low-dose A26.COV2.S vaccination did not exacerbate respiratory disease in SARS-CoV-2-inoculated Syrian hamsters with breakthrough infection. In addition, dosing down the vaccine allowed to establish that binding and neutralizing antibody titers correlate with lower respiratory tract protection probability. Overall, these preclinical data confirm efficacy of a one-dose vaccine regimen with Ad26.COV2.S in this G614 spike SARS-CoV-2 virus variant Syrian hamster model, show the added benefit of a second vaccine dose, and demonstrate that there are no signs of VAERD under conditions of suboptimal immunity.

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 Dose-dependent response to infection with SARS-CoV-2 in the ferret model: evidence of protection to re-challenge

2020 ◽  
Author(s):  
Kathryn A. Ryan ◽  
Kevin R. Bewley ◽  
Susan A. Fotheringham ◽  
Phillip Brown ◽  
Yper Hall ◽  
...  
Keyword(s):  
Rna Replication ◽  
Viral Rna ◽  
Dose Titration ◽  
High Dose ◽  
Lung Pathology ◽  
Upper Respiratory Tract ◽  
Infectious Dose ◽  
Virus Shedding ◽  
Viral Shedding ◽  
Viral Spread

AbstractIn December 2019 an outbreak of coronavirus disease (COVID-19) emerged in Wuhan, China. The causative agent was subsequently identified and named severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) which rapidly spread worldwide causing a pandemic. Currently there are no licensed vaccines or therapeutics available against SARS-CoV-2 but numerous candidate vaccines are in development and repurposed drugs are being tested in the clinic. There is a vital need for authentic COVID-19 animal models to further our understanding of pathogenesis and viral spread in addition to pre-clinical evaluation of candidate interventions.Here we report a dose titration study of SARS-CoV-2 to determine the most suitable infectious dose to use in the ferret model. We show that a high (5×106 pfu) and medium (5×104 pfu) dose of SARS-CoV-2 induces consistent upper respiratory tract (URT) viral RNA shedding in both groups of six challenged animals, whilst a low dose (5×102 pfu) resulted in only one of six displaying signs of URT viral RNA replication. The URT shedding lasted up to 21 days in the high dose animals with intermittent positive signal from day 14. Sequential culls revealed distinct pathological signs of mild multifocal bronchopneumonia in approximately 5-15% of the lung, observed on day 3 in high and medium dosed animals, with presence of mild broncho-interstitial pneumonia on day 7 onwards. No obvious elevated temperature or signs of coughing or dyspnoea were observed although animals did present with a consistent post-viral fatigue lasting from day 9-14 in the medium and high dose groups. After virus shedding ceased, re-challenged ferrets were shown to be fully protected from acute lung pathology. The endpoints of URT viral RNA replication in addition to distinct lung pathology and post viral fatigue were observed most consistently in the high dose group. This ferret model of SARS-CoV-2 infection presents a mild clinical disease (as displayed by 80% of patients infected with SARS-CoV-2). In addition, intermittent viral shedding on days 14-21 parallel observations reported in a minority of clinical cases.

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