Comparison of the pathogenicity and virus shedding of SARS CoV-2 VOC 202012/01 and D614G variant in hamster model

AbstractThe emergence of SARS-CoV-2 variants has posed a serious challenge to public health system and vaccination programs across the globe. We have studied the pathogenicity and virus shedding pattern of the SARS-CoV-2 VOC 202012/01 and compared with D614G variant in Syrian hamsters. VOC 202012/01 could produce disease in hamsters characterized by body weight loss and respiratory tract tropism but mild lung pathology. Further, we also documented that neutralizing antibodies developed against VOC 202012/01 could equally neutralize D614G variant. Higher load of VOC 202012/01 in the nasal wash specimens was observed during the first week of infection outcompeting the D614G variant. The findings suggest increased fitness of VOC 202012/01 to the upper respiratory tract which could lead to higher transmission. Further investigations are needed to understand the transmissibility of new variants.One-Sentence SummarySARS-CoV-2 VOC 202012/01 infected hamsters demonstrated high viral RNA shedding through the nasal secretions and significant body weight loss with mild lung pathology compared to the D614G variant.

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The B.1.427/1.429 (epsilon) SARS-CoV-2 variants are more virulent than ancestral B.1 (614G) in Syrian hamsters

10.1101/2021.08.25.457626 ◽

2021 ◽

Author(s):

Timothy Carroll ◽

Douglas Fox ◽

Neeltje van Doremalen ◽

Erin Ball ◽

Mary Kate Morris ◽

...

Keyword(s):

Weight Loss ◽

Body Weight ◽

Severe Disease ◽

Body Weight Loss ◽

Relative Fitness ◽

Lung Pathology ◽

Upper Respiratory Tract ◽

Hamster Model ◽

Syrian Hamsters

As novel SARS-CoV-2 variants continue to emerge, it is critical that their potential to cause severe disease and evade vaccine-induced immunity is rapidly assessed in humans and studied in animal models. In early January 2021, a novel variant of concern (VOC) designated B.1.429 comprising 2 lineages, B.1.427 and B.1.429, was originally detected in California (CA) and shown to enhance infectivity in vitro and decrease antibody neutralization by plasma from convalescent patients and vaccine recipients. Here we examine the virulence, transmissibility, and susceptibility to pre-existing immunity for B 1.427 and B 1.429 in the Syrian hamster model. We find that both strains exhibit enhanced virulence as measured by increased body weight loss compared to hamsters infected with ancestral B.1 (614G), with B.1.429 causing the most body weight loss among all 3 lineages. Faster dissemination from airways to parenchyma and more severe lung pathology at both early and late stages were also observed with B.1.429 infections relative to B.1. (614G) and B.1.427 infections. In addition, subgenomic viral RNA (sgRNA) levels were highest in oral swabs of hamsters infected with B.1.429, however sgRNA levels in lungs were similar in all three strains. This demonstrates that B.1.429 replicates to higher levels than ancestral B.1 (614G) or B.1.427 in the upper respiratory tract (URT) but not in the lungs. In multi-virus in-vivo competition experiments, we found that epsilon (B.1.427/B.1.429) and gamma (P.1) dramatically outcompete alpha (B.1.1.7), beta (B.1.351) and zeta (P.2) in the lungs. In the URT gamma, and epsilon dominate, but the highly infectious alpha variant also maintains a moderate size niche. We did not observe significant differences in airborne transmission efficiency among the B.1.427, B.1.429 and ancestral B.1 (614G) variants in hamsters. These results demonstrate enhanced virulence and high relative fitness of the epsilon (B.1.427/B.1.429) variant in Syrian hamsters compared to an ancestral B.1 (614G) strain.

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

10.1101/2021.06.25.449990 ◽

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.

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Immunogenicity and protective efficacy of BBV152: a whole virion inactivated SARS CoV-2 vaccine in the Syrian hamster model

10.21203/rs.3.rs-76768/v1 ◽

2020 ◽

Cited By ~ 1

Author(s):

Sreelekshmy Mohandas ◽

Pragya D Yadav ◽

Anita Shete ◽

Priya Abraham ◽

Krishna Mohan ◽

...

Keyword(s):

Immune Response ◽

Respiratory Tract ◽

Neutralizing Antibodies ◽

Protective Efficacy ◽

Effective Vaccine ◽

Lung Pathology ◽

Upper Respiratory Tract ◽

Hamster Model ◽

Humoral Immune ◽

Robust Immune Response

Abstract The availability of a safe and effective vaccine would be the eventual measure to deal with SARS-CoV-2 threat. Here, we have developed and assessed the immunogenicity and protective efficacy of an inactivated SARS-CoV-2 vaccine (BBV152) in hamsters. Three dose vaccination regime with three formulations of BBV152 induced significant titres of SARS-CoV-2 specific IgG and neutralizing antibodies. The formulation with imidazoquinoline adsorbed on alum adjuvant remarkably generated a quick and robust immune response. Th1 biased immune response was demonstrated by the detection of IgG2 antibodies. Post-SARS-CoV-2 infection, vaccinated hamsters did not show any histopathological changes in the lungs. The protection of the hamsters was evident by the rapid clearance of the virus from lower respiratory tract, reduced virus load in upper respiratory tract, absence of lung pathology and robust humoral immune response. These findings confirm the immunogenic potential of BBV152 and further protection of hamsters challenged with SARS-CoV-2.

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Effect of Prophylactic Use of Intranasal Oil Formulations in the Hamster Model of COVID-19

Frontiers in Pharmacology ◽

10.3389/fphar.2021.746729 ◽

2021 ◽

Vol 12 ◽

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 ◽

Histopathological Analysis ◽

Lung Pathology ◽

Upper Respiratory Tract ◽

Hamster Model ◽

Reduced Body ◽

Upper Respiratory

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV2) infection initiates with viral entry in the 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 the entry of the virus or its internalization in the upper respiratory tract are of interest. Herein, we report the prophylactic application of two intranasal formulations provided by the National Medicinal Plant Board (NMPB), Anu oil and til tailya, in the hamster model of SARS-CoV-2 infection. Prophylactic intra-nasal instillation of these oil formulations exhibited reduced viral load in lungs and resulted in reduced body weight loss and lung-pneumonitis. In line with reduced viral load, histopathological analysis revealed a reduction in lung pathology in the Anu oil group as compared to the control infected group. However, the 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 cytokine genes, including Th1 and Th17 cytokines for both the intranasal formulations as a result of decreased viral load. Together, the prophylactic intranasal application of Anu oil seems to be useful in limiting both viral load and severity in SARS-CoV2 infection in the hamster model.

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A Spike protein-based subunit SARS-CoV-2 vaccine for pets: safety, immunogenicity, and protective efficacy in juvenile cats

10.21203/rs.3.rs-1083984/v1 ◽

2021 ◽

Author(s):

Kairat Tabynov ◽

Madiana Orynbassar ◽

Leila Yelchibayeva ◽

Nurkeldi Turebekov ◽

Toktassyn Yerubayev ◽

...

Keyword(s):

Respiratory Tract ◽

Neutralizing Antibodies ◽

Large Scale ◽

Protective Efficacy ◽

Spike Protein ◽

Wild Type Virus ◽

Upper Respiratory Tract ◽

Wild Type ◽

Serum Samples ◽

Virus Shedding

Abstract Whereas multiple vaccine types have been developed to curb the spread of Severe Acute Respiratory Syndrome Coronavirus-2 (SARS-CoV-2) among humans, there are very few vaccines being developed for animals including pets. To combat the threat of human-to-animal, animal-to-animal and animal-to-human transmission and the generation of new virus variants, we developed a subunit SARS-CoV-2 vaccine which is based on recombinant spike protein extracellular domain expressed in insect cells then formulated with appropriate adjuvants. Sixteen 8-12-week-old outbred female and male kittens (n=4/group) were randomly assigned into four treatment groups: Group 1, Antigen alone; Group 2, Sepivac SWE™ adjuvant; Group 3, aluminum hydroxide adjuvant; Group 4, PBS administered control animals. All animals were vaccinated twice at day 0 and 14, intramuscularly in a volume of 0.5 mL (Groups 1-3: 5 µg of Spike protein). On days 0 and 28 serum samples were collected to evaluate anti-spike IgG, inhibition of spike binding to angiotensin-converting enzyme 2 (ACE-2), neutralizing antibodies to Wuhan-01 SARS-CoV-2 D614G (wild-type) and Delta variant viruses, and whole blood for hematology studies. At day 28, all groups were challenged with SARS-CoV-2 wild-type virus 106 TCID50 intranasally. On day 31, tissue samples (lung, heart, and nasal turbinates) were collected for histology, viral RNA detection and virus titration. Parameters evaluated in this study included safety, immunogenicity, and protection from infection with wild-type SARS-CoV-2 virus. After two immunizations, both vaccines induced high titers of serum anti-spike IgG, ACE-2 binding inhibitory and neutralizing antibodies against both wild-type and Delta variant virus in the juvenile cats. Both subunit vaccines provided protection of juvenile cats against virus shedding from the upper respiratory tract, and against viral replication in the lower respiratory tract and hearts. These promising data warrant ongoing evaluation of the vaccine’s ability to protect cats against SARS-CoV-2 Delta variant and in particular to prevent transmission of the infection to naïve cats, before proceeding with large-scale field trials.

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

PLoS Pathogens ◽

10.1371/journal.ppat.1009383 ◽

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.

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

10.1101/2021.01.19.427373 ◽

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.

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