ChAdOx1 nCoV-19 (AZD1222) or nCoV-19-Beta (AZD2816) protect Syrian hamsters against Beta Delta and Omicron variants

Doremalen, Neeltje van; Schulz, Jonathan; Adney, Danielle R.; Saturday, Taylor A.; Fischer, Robert J.; Yinda, Claude Kwe; Thakur, Nazia; Newman, Joseph; Ulaszewska, Marta; Belij‐Rammerstorfer, Sandra; Saturday, Greg; Spencer, Alexandra J.; Bailey, Dalan; Russell, Colin A.; Gilbert, Sarah C.; Lambe, Teresa; Munster, Vincent J.

doi:10.1038/s41467-022-32248-6

Cited by 32 publications

(21 citation statements)

References 49 publications

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“…Nonetheless, the Omicron VOC has replaced the Delta VOC in the human population, and our study was not designed to address this question. Omicron is antigenically the most distant VOC (18), and recent studies suggest that Omicron variants can readily overcome immunity acquired from previous infection with earlier variants and vaccination (19)(20)(21)(22)(23). The rise in Omicron cases could be a combination of immune evasion, waning immunity, relaxation of coronavirus disease-related restrictions, and other factors that may affect transmission, such as reduced symptoms caused by Omicron, resulting in prolonged contact with other humans.…”

Section: Discussionmentioning

confidence: 99%

SARS-CoV-2 Omicron BA.1 and BA.2 are attenuated in rhesus macaques as compared to Delta

et al. 2022

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Since the emergence of SARS-CoV-2, five different variants of concern (VOCs) have been identified: Alpha, Beta, Gamma, Delta, and Omicron. Because of confounding factors in the human population, such as preexisting immunity, comparing severity of disease caused by different VOCs is challenging. Here, we investigate disease progression in the rhesus macaque model upon inoculation with the Delta, Omicron BA.1, and Omicron BA.2 VOCs. Disease severity in rhesus macaques inoculated with Omicron BA.1 or BA.2 was lower than those inoculated with Delta and resulted in significantly lower viral loads in nasal swabs, bronchial cytology brush samples, and lung tissue in rhesus macaques. Cytokines and chemokines were up-regulated in nasosorption samples of Delta animals compared to Omicron BA.1 and BA.2 animals. Overall, these data suggest that, in rhesus macaques, Omicron replicates to lower levels than the Delta VOC, resulting in reduced clinical disease.

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Section: Discussionmentioning

confidence: 99%

SARS-CoV-2 Omicron BA.1 and BA.2 are attenuated in rhesus macaques as compared to Delta

et al. 2022

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“…At the time of emergence of Delta, a large part of the human population was either previously exposed to and/or vaccinated, the underlying immune status might have played a role in providing additional selective pressure. Analyses of the cross-neutralization between Alpha and Delta suggest subtly different antigenic profiles [37]. Two VOC with similar phenotype, as observed here for Alpha and Delta, would theoretically be more likely to be transmitted as a mixed-variant population.…”

Section: Discussionmentioning

confidence: 78%

Host and viral determinants of airborne transmission of SARS-CoV-2 in the Syrian hamster

Port

Morris

Yinda

et al. 2022

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Airborne transmission is one of the major routes contributing to the spread of SARS-CoV-2. Successful aerosol transmission occurs when people release respiratory particles carrying infectious virus in the fine aerosol size range. It remains poorly understood how infection influences the physiological host factors that are integral to this process. Here we assessed the changes in breathing, exhaled droplets, and released virus early after infection with the Alpha and Delta variants in the Syrian hamster. Infection with the two variants led to only nuanced differences in viral tissue titers, disease severity, or shedding magnitude. Both variants led to a short window of detectable virus in the air between 24 h and 48 h, which was poorly reflected by upper respiratory shedding measured in oropharyngeal swabs. The loss of viable air samples coincided with changes in airway constriction as measured by whole body plethysmography, and a decrease of fine aerosols produced in the 1-10 μm aerodynamic diameter range. We found that male sex was associated with greater viral replication in the upper respiratory tract and virus shedding in the air. This coincided with an exhaled particle profile shifted towards smaller droplets, independent of variant. Transmission efficiency of Alpha and Delta did not differ on average but exhibited clear variation among donor individuals, including a superspreading event. Transmission leading to substantial dual infections only occurred when both viruses were shed by the same donor and exposure was prolonged. These findings provide direct experimental evidence that quantitative and qualitative assessment of exhaled aerosols may be critical for understanding the limitations and determinants of efficient airborne transmission, thus allowing us to control the pandemic with non-pharmaceutical interventions.

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“…Viral genome copies in the nose (representative of viral shedding) were significantly reduced but remained higher than levels observed in the lungs. In general, protection in the nose is more difficult to achieve than in the lower respiratory tract, which is more pronounced following heterologous compared with homologous virus challenge infection [ 34 , 35 , 36 , 37 ]. Differences in the BA.1 and BA.2 S protein sequence that affect nAb generation may have had an impact on nasal protection.…”

Section: Discussionmentioning

confidence: 99%

Assessment of Immunogenicity and Efficacy of CV0501 mRNA-Based Omicron COVID-19 Vaccination in Small Animal Models

et al. 2023

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Severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) Omicron and its subvariants (BA.2, BA.4, BA.5) represented the most commonly circulating variants of concern (VOC) in the coronavirus disease 2019 (COVID-19) pandemic in 2022. Despite high vaccination rates with approved SARS-CoV-2 vaccines encoding the ancestral spike (S) protein, these Omicron subvariants have collectively resulted in increased viral transmission and disease incidence. This necessitates the development and characterization of vaccines incorporating later emerging S proteins to enhance protection against VOC. In this context, bivalent vaccine formulations may induce broad protection against VOC and potential future SARS-CoV-2 variants. Here, we report preclinical data for a lipid nanoparticle (LNP)-formulated RNActive® N1-methylpseudouridine (N1mΨ) modified mRNA vaccine (CV0501) based on our second-generation SARS-CoV-2 vaccine CV2CoV, encoding the S protein of Omicron BA.1. The immunogenicity of CV0501, alone or in combination with a corresponding vaccine encoding the ancestral S protein (ancestral N1mΨ), was first measured in dose-response and booster immunization studies performed in Wistar rats. Both monovalent CV0501 and bivalent CV0501/ancestral N1mΨ immunization induced robust neutralizing antibody titers against the BA.1, BA.2 and BA.5 Omicron subvariants, in addition to other SARS-CoV-2 variants in a booster immunization study. The protective efficacy of monovalent CV0501 against live SARS-CoV-2 BA.2 infection was then assessed in hamsters. Monovalent CV0501 significantly reduced SARS-CoV-2 BA.2 viral loads in the airways, demonstrating protection induced by CV0501 vaccination. CV0501 has now advanced into human Phase 1 clinical trials (ClinicalTrials.gov Identifier: NCT05477186).

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ChAdOx1 nCoV-19 (AZD1222) or nCoV-19-Beta (AZD2816) protect Syrian hamsters against Beta Delta and Omicron variants

Cited by 32 publications

References 49 publications

SARS-CoV-2 Omicron BA.1 and BA.2 are attenuated in rhesus macaques as compared to Delta

SARS-CoV-2 Omicron BA.1 and BA.2 are attenuated in rhesus macaques as compared to Delta

Host and viral determinants of airborne transmission of SARS-CoV-2 in the Syrian hamster

Assessment of Immunogenicity and Efficacy of CV0501 mRNA-Based Omicron COVID-19 Vaccination in Small Animal Models

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