Animal Models for COVID-19: Hamsters, Mouse, Ferret, Mink, Tree Shrew, and Non-human Primates

Shou, Shuyu; Liu, Menghui; Yang, Yang; Kang, Ning; Song, Yingying; Tan, Dan; Liu, Nannan; Wang, Feifei; Liu, Jing; Xie, Youhua

doi:10.3389/fmicb.2021.626553

Cited by 102 publications

(97 citation statements)

References 126 publications

(224 reference statements)

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“…Many nonhuman primate species including rhesus macaques (Macaca mulatta), cynomolgus macaques (Macaca fascicularis), African green monkeys (Chlorocebus aethiops) and pigtail macaques reported here (Macaca nemestrina), have been critical for investigating COVID-19 disease and pre-clinical testing of COVID-19 vaccines (31,32). Recent findings from Melton et al, demonstrate moderate SARS-CoV-2 disease in pigtail macaques (33), as compared to the more mild disease observed in rhesus macaques, but with similar levels of viral load in respiratory mucosa between the two species (34).…”

Section: Discussionmentioning

confidence: 99%

A Single Dose SARS-CoV-2 Replicon RNA Vaccine Induces Cellular and Humoral Immune Responses in Simian Immunodeficiency Virus Infected and Uninfected Pigtail Macaques

et al. 2021

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The ongoing COVID-19 vaccine rollout is critical for reducing SARS-CoV-2 infections, hospitalizations, and deaths worldwide. Unfortunately, massive disparities exist in getting vaccines to vulnerable populations, including people living with HIV. Preliminary studies indicate that COVID-19 mRNA vaccines are safe and immunogenic in people living with HIV that are virally suppressed with potent antiretroviral therapy but may be less efficacious in immunocompromised individuals. This raises the concern that COVID-19 vaccines may be less effective in resource poor settings with limited access to antiretroviral therapy. Here, we evaluated the immunogenicity of a single dose COVID-19 replicon RNA vaccine expressing Spike protein (A.1) from SARS-CoV-2 (repRNA-CoV2S) in immunocompromised, SIV infected and immune competent, naïve pigtail macaques. Moderate vaccine-specific cellular Th1 T-cell responses and binding and neutralizing antibodies were induced by repRNA-CoV2S in SIV infected animals and naïve animals. Furthermore, vaccine immunogenicity was elicited even among the animals with the highest SIV viral burden or lowest peripheral CD4 counts prior to immunization. This study provides evidence that a SARS-CoV-2 repRNA vaccine could be employed to induce strong immunity against COVID-19 in HIV infected and other immunocompromised individuals.

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Section: Discussionmentioning

confidence: 99%

A Single Dose SARS-CoV-2 Replicon RNA Vaccine Induces Cellular and Humoral Immune Responses in Simian Immunodeficiency Virus Infected and Uninfected Pigtail Macaques

et al. 2021

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“…Animal models that are susceptible to several human respiratory viruses, such as ferrets and golden Syrian hamsters, are also valuable to evaluate the effects of concurrent and sequential viral infections on disease severity, immune response and the mechanisms of virus‒virus interaction at the host level ( 16 ). However, the immune response against human respiratory viruses and the mechanisms of immune evasion might differ between animal models and humans, which constitutes a potential limitation.…”

Section: Advantages and Limitations Of Ex Vivo And In Vivo Modelsmentioning

confidence: 99%

Viral Interference between Respiratory Viruses

Piret¹,

Boivin²

2022

Emerg. Infect. Dis.

171

114

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Multiple respiratory viruses can concurrently or sequentially infect the respiratory tract and lead to virus‒virus interactions. Infection by a first virus could enhance or reduce infection and replication of a second virus, resulting in positive (additive or synergistic) or negative (antagonistic) interaction. The concept of viral interference has been demonstrated at the cellular, host, and population levels. The mechanisms involved in viral interference have been evaluated in differentiated airway epithelial cells and in animal models susceptible to the respiratory viruses of interest. A likely mechanism is the interferon response that could confer a temporary nonspecific immunity to the host. During the coronavirus disease pandemic, nonpharmacologic interventions have prevented the circulation of most respiratory viruses. Once the sanitary restrictions are lifted, circulation of seasonal respiratory viruses is expected to resume and will offer the opportunity to study their interactions, notably with severe acute respiratory syndrome coronavirus 2.

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“…Uncontrolled induction of inflammation is one of the hallmarks of pathology after infection with SARS-CoV-2 16 . Therefore, the lungs of the vaccinated and control animals were assayed for cytokine (IFN-γ, IFN-α, IL-10, IL-6, IL-4, IL-2, IL-21, IL-17, TGF-β1, TNF-α) and chemokine (CCL5, CCL3) expression by qRT-PCR (Primer and probe sequences, Table S2), normalized to γ-actin and expressed as fold-changes over the average expression of three uninfected, unchallenged hamsters.…”

Section: Resultsmentioning

confidence: 99%

“…By day 14 p.c., the inflammation was completely cleared in the vaccinated animals and significantly reduced in the control unvaccinated group, and the antigen was absent in the lungs of both groups, which is a common feature of the hamster model. The hamster model is well established for SARS CoV-2 as it mimics the human lung pathology seen in COVID-19 patients 16 . This study concludes that SARS CoV-2 challenged CORAVAX vaccinated animals never developed the severe inflammation associated with the disease (compared with the control animals).…”

Section: Discussionmentioning

confidence: 99%

A single-dose of the deactivated rabies virus vectored COVID-19 vaccine, CORAVAX, is highly efficacious and alleviates lung inflammation in the hamster model

Schnell

2022

Preprint

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Without sufficient herd immunity through either vaccination or natural infection, the Coronavirus Disease 2019 pandemic is unlikely to be controlled. Waning immunity with the currently approved vaccines suggests the need to evaluate vaccines causing the induction of long-term responses. Here we report the immunogenicity and efficacy of our adjuvanted single-dose Rabies vectored SARS CoV-2 S1 vaccine, CORAVAX, in hamsters. CORAVAX induces high SARS CoV-2 S1 specific and virus-neutralizing antibodies (VNA) that prevent weight loss, viral loads, disease, lung inflammation, and the cytokine storm in hamsters. We also observed high Rabies VNA titers. In summary, CORAVAX is a promising dual antigen vaccine candidate for clinical evaluation against SARS CoV-2 and Rabies virus.

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Animal Models for COVID-19: Hamsters, Mouse, Ferret, Mink, Tree Shrew, and Non-human Primates

Cited by 102 publications

References 126 publications

A Single Dose SARS-CoV-2 Replicon RNA Vaccine Induces Cellular and Humoral Immune Responses in Simian Immunodeficiency Virus Infected and Uninfected Pigtail Macaques

A Single Dose SARS-CoV-2 Replicon RNA Vaccine Induces Cellular and Humoral Immune Responses in Simian Immunodeficiency Virus Infected and Uninfected Pigtail Macaques

Viral Interference between Respiratory Viruses

A single-dose of the deactivated rabies virus vectored COVID-19 vaccine, CORAVAX, is highly efficacious and alleviates lung inflammation in the hamster model

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