ChAdOx1 nCoV-19 (AZD1222) protects Syrian hamsters against SARS-CoV-2 B.1.351 and B.1.1.7

Fischer, Robert J.; Doremalen, Neeltje van; Adney, Danielle R.; Yinda, Claude Kwe; Port, Julia R; Holbrook, Myndi G.; Schulz, Jonathan; Williamson, Brandi N.; Thomas, Tina; Barbian, Kent D.; Anzick, Sarah L.; Ricklefs, Stacy M.; Smith, Brian J; Long, Dan; Martens, Craig; Saturday, Greg; Wit, Emmie de; Gilbert, Sarah C.; Lambe, Teresa; Munster, Vincent J.

doi:10.1101/2021.03.11.435000

Cited by 39 publications

(41 citation statements)

References 36 publications

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“…Importantly, previous infection may not give ongoing protection against VOC months later, and people with asymptomatic infection had lower responses at all time points across many of the immune parameters we measured. Maintenance of immune memory over time is critically required for the effective neutralisation of VOC that is most likely to confer sterilising immunity, whilst other immune mechanisms including non-neutralising antibodies and T cells may account for the protection against severe disease, including for VOC 57,58,59,60 . This study provides a basis for more targeted vaccination programme of previously infected individuals based on early immunological signature 28 days after infection.…”

Section: Discussionmentioning

confidence: 99%

Divergent trajectories of antiviral memory after SARS-Cov-2 infection

Tomić¹,

Skelly²,

Ogbe³

et al. 2021

Preprint

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Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection is normally controlled by effective host immunity including innate, humoral and cellular responses. However, the trajectories and correlates of acquired immunity, and the capacity of memory responses months after infection to neutralise variants of concern - which has important public health implications - is not fully understood. To address this, we studied a cohort of 78 UK healthcare workers who presented in April to June 2020 with symptomatic PCR-confirmed infection or who tested positive during an asymptomatic screening programme and tracked virus-specific B and T cell responses longitudinally at 5-6 time points each over 6 months, prior to vaccination. We observed a highly variable range of responses, some of which - T cell interferon-gamma (IFN-γ) ELISpot, N-specific antibody waned over time across the cohort, while others (spike-specific antibody, B cell memory ELISpot) were stable. In such cohorts, antiviral antibody has been linked to protection against re-infection. We used integrative analysis and a machine-learning approach (SIMON - Sequential Iterative Modeling Over Night) to explore this heterogeneity and to identify predictors of sustained immune responses. Hierarchical clustering defined a group of high and low antibody responders, which showed stability over time regardless of clinical presentation. These antibody responses correlated with IFN-γ ELISpot measures of T cell immunity and represent a subgroup of patients with a robust trajectory for longer term immunity. Importantly, this immune-phenotype associates with higher levels of neutralising antibodies not only against the infecting (Victoria) strain but also against variants B.1.1.7 (alpha) and B.1.351 (beta). Overall memory responses to SARS-CoV-2 show distinct trajectories following early priming, that may define subsequent protection against infection and severe disease from novel variants.

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Section: Discussionmentioning

confidence: 99%

Divergent trajectories of antiviral memory after SARS-Cov-2 infection

Tomić¹,

Skelly²,

Ogbe³

et al. 2021

Preprint

Self Cite

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“…Of note, we observed strong neutralizing responses in the 10 μg, 2-dose regimen groups that were similar across WA1, B.1.1.7 and B.1.351 variants. This is particularly encouraging as many studies have demonstrated decreased neutralizing antibody responses of convalescent or vaccinee sera, in particular against B.1.35 4,11,14,16,27 . hACE2-RBD binding inhibition levels mirrored overall humoral responses.…”

Section: Discussionmentioning

confidence: 85%

“…The development of effective and safe vaccines in response to the SARS-CoV-2 pandemic has occurred at an unprecedented rate. This success has been tempered by the reduced vaccine efficacy against some emerging VOCs, most notably B.1.351 4,5,8,11,13,16,27 . The need for more broadly effective vaccines against multiple lineages of SARS-CoV-2 will likely increase, as underscored by the rapid rise of VOCs in India, including B.1.1.7 and emerging variants B.1.617 with derivative lineages, and B.1.618 3 .…”

Section: Discussionmentioning

confidence: 99%

“…Publically available preprint reports have recently shown that the vaccines being marketed by AstraZeneca, ChAdOx1 nCoV-19 (AZD1222), and Moderna, mRNA-1273, show protection against B.1.351 challenge in hamster and rhesus models, respectively 27,38 . Another preprint describes protection from B.1.351 challenge in human ACE2 transgenic mice vaccinated with the CureVac mRNA vaccine, CVnCoV 39 .…”

Section: Discussionmentioning

confidence: 99%

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A SARS-CoV-2 spike ferritin nanoparticle vaccine protects against heterologous challenge with B.1.1.7 and B.1.351 virus variants in Syrian golden hamsters

Wuertz

Barkei

Chen

et al. 2021

Preprint

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The emergence of SARS-CoV-2 variants of concern (VOC) requires adequate coverage of vaccine protection. We evaluated whether a spike ferritin nanoparticle vaccine (SpFN), adjuvanted with the Army Liposomal Formulation QS21 (ALFQ), conferred protection against the B.1.1.7 and B.1.351 VOCs in Syrian golden hamsters. SpFN-ALFQ was administered as either single or double-vaccination (0 and 4 week) regimens, using a high (10 μg) or low (0.2 μg) immunogen dose. Animals were intranasally challenged at week 11. Binding antibody responses were comparable between high- and low-dose groups. Neutralizing antibody titers were equivalent against WA1, B.1.1.7, and B.1.351 variants following two high dose two vaccinations. SpFN-ALFQ vaccination protected against SARS-CoV-2-induced disease and viral replication following intranasal B.1.1.7 or B.1.351 challenge, as evidenced by reduced weight loss, lung pathology, and lung and nasal turbinate viral burden. These data support the development of SpFN-ALFQ as a broadly protective, next-generation SARS-CoV-2 vaccine.

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“… 16 A 9.5-fold reduction in the virus neutralizing antibody titer was observed in AZD1222 vaccinated (Oxford-AstraZeneca) hamster sera against B.1.351 compared with B.1.1.7. 17 The AZD1222 vaccine efficacy against mild-to-moderate COVID-19 due to the B.1.351 variant was reported to be only 10.4%. 18 The variant is refractory to neutralization by most monoclonal antibodies targeting N-terminal domain and receptor-binding motif on RBD due to the E484K mutation.…”

mentioning

confidence: 99%

Emerging SARS-CoV-2 variants: impact on vaccine efficacy and neutralizing antibodies

Sharun

Tiwari

Dhama

et al. 2021

Human Vaccines & Immunotherapeutics

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The genetic variants of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) have been emerging and circulating in different parts of the world from the beginning of the coronavirus disease (COVID-19) pandemic. Variants are divided into three classes: variant of interest, variant of concern, and variant of high consequence depending on its impact on the transmission, disease severity, diagnostics, vaccines, and therapeutics. The variants of concern include the United Kingdom variant (B.1.1.7), South Africa variant (B.1.351), two related California variants (B.1.427 and B.1.429), and Brazil variant (P.1). These SARS-CoV-2 variants have a direct impact on the available COVID-19 vaccines and immunotherapeutics as they can alter the neutralizing activity of vaccine-elicited antibodies and monoclonal antibodies resulting in mild-to-substantial loss of efficacy. There is a need to establish surveillance systems that can monitor the emergence of novel SARS-CoV-2 variants worldwide.

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ChAdOx1 nCoV-19 (AZD1222) protects Syrian hamsters against SARS-CoV-2 B.1.351 and B.1.1.7

Cited by 39 publications

References 36 publications

Divergent trajectories of antiviral memory after SARS-Cov-2 infection

Divergent trajectories of antiviral memory after SARS-Cov-2 infection

A SARS-CoV-2 spike ferritin nanoparticle vaccine protects against heterologous challenge with B.1.1.7 and B.1.351 virus variants in Syrian golden hamsters

Emerging SARS-CoV-2 variants: impact on vaccine efficacy and neutralizing antibodies

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