SARS-CoV-2 B.1.1.7 Infection of Syrian Hamster Does Not Cause More Severe Disease, and Naturally Acquired Immunity Confers Protection

Nuñez, Ivette A.; Lien, Christopher Z.; Selvaraj, Prabhuanand; Stauft, Charles B.; Li, Shufeng; Starost, Matthew F.; Wang, Tony T.

doi:10.1128/msphere.00507-21

Cited by 24 publications

(29 citation statements)

References 15 publications

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“…The exceptions were B.1 (614G) and the P1 variant, which replicated to levels that were similar to (epsilon) B.1.427/B.1.429 in both lungs and URT; and the B.1.1.7 variant that was able to compete with B.1 (614G), B.1.427/429 and P.1 in the URT but not the lung. Our results are consistent with a previous report that the B.1.1.7 variant replicates to higher levels in the nose of Syrian hamsters than the ancestral B.1 variant [ 23 ]. Both the P.1 and B.1.1.7 variants carry the N501Y-mutation that also enhances infectivity in-vitro [ 22 ] and this may explain why they can successfully compete with the L452R variants in the nose of hamsters.…”

Section: Discussionsupporting

confidence: 94%

“…As previously reported with ancestral B.1 and other VOC [13, 23,24], in this study intranasal inoculation of hamsters with the SARS-CoV-2 B.1 (614G) or epsilon variants (B.1.247/ B.1.249) induced progressive moderate to severe broncho-interstitial pneumonia with vasculitis, beginning as early as day 2 PI. By day 10 PI, lesions were largely resolved, with only residual…”

Section: Plos Pathogenssupporting

confidence: 77%

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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

et al. 2022

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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 SARS-CoV-2 variant designated B.1.429 comprising 2 lineages, B.1.427 and B.1.429, was originally detected in California (CA) and it was shown to have enhanced infectivity in vitro and decreased 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 variants 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 marked body weight loss among the 3 variants. 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 variants. This demonstrates that B.1.429 replicates to higher levels than ancestral B.1 (614G) or B.1.427 in the oropharynx but not in the lungs. In multi-virus in-vivo competition experiments, we found that B.1. (614G), 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 nasal cavity, B.1. (614G), 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) and WA-1 variants in hamsters. These results demonstrate enhanced virulence and high relative oropharyngeal replication of the epsilon (B.1.427/B.1.429) variant in Syrian hamsters compared to an ancestral B.1 (614G) variant.

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Section: Discussionsupporting

confidence: 94%

Section: Plos Pathogenssupporting

confidence: 77%

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

et al. 2022

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“…Recent studies in mice, hamsters, and NHPs show that animals previously infected or vaccinated against lineage A SARS-CoV-2 (for example, the original Wuhan strain) [7] are protected against challenge with homologous as well as heterologous virus strains including the alpha (B.1.1.7), beta (B.1.351), gamma (B.1.1.28.1), and delta (B.1.617.2) VOCs [8][9][10][11][12][13][14]. In the NHP model, however, more viral breakthroughs were observed following beta VOC challenge as compared with homologous WA1/2020 challenge [12,15].…”

Section: Vaccine Cross-protection and Transmissionmentioning

confidence: 99%

Advances and gaps in SARS-CoV-2 infection models

et al. 2022

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The global response to Coronavirus Disease 2019 (COVID-19) is now facing new challenges such as vaccine inequity and the emergence of SARS-CoV-2 variants of concern (VOCs). Preclinical models of disease, in particular animal models, are essential to investigate VOC pathogenesis, vaccine correlates of protection and postexposure therapies. Here, we provide an update from the World Health Organization (WHO) COVID-19 modeling expert group (WHO-COM) assembled by WHO, regarding advances in preclinical models. In particular, we discuss how animal model research is playing a key role to evaluate VOC virulence, transmission and immune escape, and how animal models are being refined to recapitulate COVID-19 demographic variables such as comorbidities and age.

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“…Grading: 0 = none, 1 = mild, 2 = moderate, and 3 = severe. Each pathology category was weighted equally as previously described 24 . A graph was prepared by summing up the score in each category.…”

Section: Methodsmentioning

confidence: 99%

MVA vector expression of SARS-CoV-2 spike protein and protection of adult Syrian hamsters against SARS-CoV-2 challenge

et al. 2021

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Numerous vaccine candidates against SARS-CoV-2, the causative agent of the COVID-19 pandemic, are under development. The majority of vaccine candidates to date are designed to induce immune responses against the viral spike (S) protein, although different forms of S antigen have been incorporated. To evaluate the yield and immunogenicity of different forms of S, we constructed modified vaccinia virus Ankara (MVA) vectors expressing full-length S (MVA-S), the RBD, and soluble S ectodomain and tested their immunogenicity in dose-ranging studies in mice. All three MVA vectors induced spike-specific immunoglobulin G after one subcutaneous immunization and serum titers were boosted following a second immunization. The MVA-S and MVA-ssM elicited the strongest neutralizing antibody responses. In assessing protective efficacy, MVA-S-immunized adult Syrian hamsters were challenged with SARS-CoV-2 (USA/WA1/2020). MVA-S-vaccinated hamsters exhibited less severe manifestations of atypical pneumocyte hyperplasia, hemorrhage, vasculitis, and especially consolidation, compared to control animals. They also displayed significant reductions in gross pathology scores and weight loss, and a moderate reduction in virus shedding was observed post challenge in nasal washes. There was evidence of reduced viral replication by in situ hybridization, although the reduction in viral RNA levels in lungs and nasal turbinates did not reach significance. Taken together, the data indicate that immunization with two doses of an MVA vector expressing SARS-CoV-2 S provides protection against a stringent SARS-CoV-2 challenge of adult Syrian hamsters, reaffirm the utility of this animal model for evaluating candidate SARS-CoV-2 vaccines, and demonstrate the value of an MVA platform in facilitating vaccine development against SARS-CoV-2.

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SARS-CoV-2 B.1.1.7 Infection of Syrian Hamster Does Not Cause More Severe Disease, and Naturally Acquired Immunity Confers Protection

Cited by 24 publications

References 15 publications

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

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

Advances and gaps in SARS-CoV-2 infection models

MVA vector expression of SARS-CoV-2 spike protein and protection of adult Syrian hamsters against SARS-CoV-2 challenge

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