An S1-Nanoparticle Vaccine Protects against SARS-CoV-2 Challenge in K18-hACE2 Mice

Oosten, Linda van; Yan, Kexin; Rawle, Daniel J.; Le, Thuy T.; Altenburg, Jort J; Fougeroux, Cyrielle; Goksøyr, Louise; Jongh, Willem A. de; Nielsen, Morten A.; Sander, Adam F.; Pijlman, Gorben P.; Suhrbier, Andreas

doi:10.1128/jvi.00844-22

Cited by 7 publications

(5 citation statements)

References 10 publications

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“…These mice develop a robust respiratory disease that histologically resembles severe COVID-19 [19][20][21]. These mice have been widely used for evaluation of new interventions [22][23][24][25][26][27][28][29], and for virology and immunopathology studies [30][31][32]. However, SARS-CoV-2 infected K18-hACE2 mice show a number of differences [19], perhaps the most important difference is a fulminant brain infection that is associated with the generally lethal outcome in this model after infection with original strains of SARS-CoV-2 [33].…”

Section: Introductionmentioning

confidence: 99%

Mouse models of COVID-19 recapitulate inflammatory pathways rather than gene expression

et al. 2022

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How well mouse models recapitulate the transcriptional profiles seen in humans remains debatable, with both conservation and diversity identified in various settings. Herein we use RNA-Seq data and bioinformatics approaches to analyze the transcriptional responses in SARS-CoV-2 infected lungs, comparing 4 human studies with the widely used K18-hACE2 mouse model, a model where hACE2 is expressed from the mouse ACE2 promoter, and a model that uses a mouse adapted virus and wild-type mice. Overlap of single copy orthologue differentially expressed genes (scoDEGs) between human and mouse studies was generally poor (≈15–35%). Rather than being associated with batch, sample treatment, viral load, lung damage or mouse model, the poor overlaps were primarily due to scoDEG expression differences between species. Importantly, analyses of immune signatures and inflammatory pathways illustrated highly significant concordances between species. As immunity and immunopathology are the focus of most studies, these mouse models can thus be viewed as representative and relevant models of COVID-19.

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Section: Introductionmentioning

confidence: 99%

Mouse models of COVID-19 recapitulate inflammatory pathways rather than gene expression

et al. 2022

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“…Neutralizing antibody titers were determined for a selection of purified mAbs using Vero E6 cells and a CPE-based assay in 96 well plates [ 19 , 21 ], with the flavivirus specific mAb 4G2 used as a negative control. Neutralization curves against an original strain isolate, SARS-CoV-2 QLD02 , are provided; SCV2-5A1 and SCV2-3H9 showed the highest potency with the concentrations of mAb providing 50% neutralization (IC50) at ≈3 and 0.35 µg/mL, respectively ( Figure 5 ).…”

Section: Resultsmentioning

confidence: 99%

“…The inactivated virus was partially purified using a 20% sucrose cushion [ 19 ], protein concentration determined by Bradford Assay (Bio-Rad, Hercules, CA, USA), and was adjuvanted with QS-21 and 3-O-desacyl-4′-monophosphoryl lipid A as described [ 20 ]. After ≈2 months neutralization activity of serum against SARS-CoV-2 QLD02 was confirmed [ 19 , 21 ]. Mice received a further 87 µg of UVC-inactivated, sucrose cushion purified, SARS-CoV-2 QLD02 in PBS (no adjuvant), delivered i.v.…”

Section: Methodsmentioning

confidence: 99%

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Monoclonal Antibodies Specific for SARS-CoV-2 Spike Protein Suitable for Multiple Applications for Current Variants of Concern

Morgan

Yan

et al. 2022

Viruses

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The global coronavirus disease 2019 (COVID-19) pandemic caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has spawned an ongoing demand for new research reagents and interventions. Herein we describe a panel of monoclonal antibodies raised against SARS-CoV-2. One antibody showed excellent utility for immunohistochemistry, clearly staining infected cells in formalin-fixed and paraffin embedded lungs and brains of mice infected with the original and the omicron variants of SARS-CoV-2. We demonstrate the reactivity to multiple variants of concern using ELISAs and describe the use of the antibodies in indirect immunofluorescence assays, Western blots, and rapid antigen tests. Finally, we illustrate the ability of two antibodies to reduce significantly viral tissue titers in K18-hACE2 transgenic mice infected with the original and an omicron isolate of SARS-CoV-2.

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“…S1), and we established a sensitive BNT162b2 dose in mice. BNT162b2 has been delivered to adult mice at a dose of 0.2 to 10 μg of encapsulated mRNA (33)(34)(35)(36)(37)(38)(39)(40)(41). We evaluated 0.05 to 5.0 μg of BNT162b2 in mice (fig.…”

Section: Establishing a Sensitive Murine Antigen Dose To Adjuvantmentioning

confidence: 99%

Adjuvantation of a SARS-CoV-2 mRNA vaccine with controlled tissue-specific expression of an mRNA encoding IL-12p70

Brook,

Duval,

Barman

et al. 2024

Sci. Transl. Med.

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Messenger RNA (mRNA) vaccines were pivotal in reducing severe acute respiratory syndrome 2 (SARS-CoV-2) infection burden, yet they have not demonstrated robust durability, especially in older adults. Here, we describe a molecular adjuvant comprising a lipid nanoparticle (LNP)–encapsulated mRNA encoding interleukin-12p70 (IL-12p70). The bioactive adjuvant was engineered with a multiorgan protection (MOP) sequence to restrict transcript expression to the intramuscular injection site. Admixing IL-12–MOP (CTX-1796) with the BNT162b2 SARS-CoV-2 vaccine increased spike protein–specific immune responses in mice. Specifically, the benefits of IL-12–MOP adjuvantation included amplified humoral and cellular immunity and increased immune durability for 1 year after vaccination in mice. An additional benefit included the restoration of immunity in aged mice to amounts comparable to those achieved in young adult animals, alongside amplification with a single immunization. Associated enhanced dendritic cell and germinal center responses were observed. Together, these data demonstrate that an LNP-encapsulated IL-12–MOP mRNA-encoded adjuvant can amplify immunogenicity independent of age, demonstrating translational potential to benefit vulnerable populations.

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An S1-Nanoparticle Vaccine Protects against SARS-CoV-2 Challenge in K18-hACE2 Mice

Cited by 7 publications

References 10 publications

Mouse models of COVID-19 recapitulate inflammatory pathways rather than gene expression

Mouse models of COVID-19 recapitulate inflammatory pathways rather than gene expression

Monoclonal Antibodies Specific for SARS-CoV-2 Spike Protein Suitable for Multiple Applications for Current Variants of Concern

Adjuvantation of a SARS-CoV-2 mRNA vaccine with controlled tissue-specific expression of an mRNA encoding IL-12p70

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