Exosomes decorated with a recombinant SARS-CoV-2 receptor-binding domain as an inhalable COVID-19 vaccine

Wang, Zhenzhen; Popowski, Kristen D.; Zhu, Dashuai; Abad, Blanca López de Juan; Wang, Xianyun; Liu, Mengrui; Lutz, Halle; Naeyer, Nicole De; DeMarco, C. Todd; Denny, Thomas N.; Dinh, Phuong‐Uyen; Li, Zhenhua; Cheng, Ke

doi:10.1038/s41551-022-00902-5

Cited by 168 publications

(116 citation statements)

References 63 publications

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“…Using ghosts of the EVs RBD , which should not contain any biomolecular content (proteins or genetic material), may provide an alternative if any safety concern is raised in the future, as these ghosts should preserve the outer membrane feature of the EVs and, thus, their targeting capabilities. Also note that a very recent report showed that lung-derived EVs, 36 which were chemically conjugated to RBD, had no safety concerns of such types of viruslike EVs 52 and strengthen the potentiality of the proposed EVs RBD to be used in vivo in other studies.…”

Section: Resultsmentioning

confidence: 69%

“… 25 − 28 Third, EVs share important similarities with enveloped viruses, including comparable sizes and host membrane compositions. 20 , 29 − 31 EVs are thus attractive noninfectious vehicles for examination of viral uptake pathways of cellular cargo delivery, 25 , 32 − 34 or for the development of EV-based vaccines 35 , 36 and related adjuvants. 37 For example, EVs presenting the coronavirus S protein or its RBD were proposed as potential vaccines already in the mid-2000s for SARS-CoV 38 as well as for the current SARS-CoV-2 pandemic.…”

Section: Introductionmentioning

confidence: 99%

“… 37 For example, EVs presenting the coronavirus S protein or its RBD were proposed as potential vaccines already in the mid-2000s for SARS-CoV 38 as well as for the current SARS-CoV-2 pandemic. 36 , 39 , 40 Moreover, they showed efficiency as decoys for neutralizing antibodies 41 and as systems for targeted delivery of antiviral agents. 42 In addition, the ease at which EVs can be genetically engineered makes these formulations ideal for rapid studies of emerging viral mutations as they appear.…”

Section: Introductionmentioning

confidence: 99%

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Genetically Engineered MRI-Trackable Extracellular Vesicles as SARS-CoV-2 Mimetics for Mapping ACE2 Binding In Vivo

et al. 2022

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The elucidation of viral-receptor interactions and an understanding of virus-spreading mechanisms are of great importance, particularly in the era of a pandemic. Indeed, advances in computational chemistry, synthetic biology, and protein engineering have allowed precise prediction and characterization of such interactions. Nevertheless, the hazards of the infectiousness of viruses, their rapid mutagenesis, and the need to study viral-receptor interactions in a complex in vivo setup call for further developments. Here, we show the development of biocompatible genetically engineered extracellular vesicles (EVs) that display the receptor binding domain (RBD) of SARS-CoV-2 on their surface as coronavirus mimetics (EVs RBD ). Loading EVs RBD with iron oxide nanoparticles makes them MRI-visible and, thus, allows mapping of the binding of RBD to ACE2 receptors noninvasively in live subjects. Moreover, we show that EVs RBD can be modified to display mutants of the RBD of SARS-CoV-2, allowing rapid screening of currently raised or predicted variants of the virus. The proposed platform thus shows relevance and cruciality in the examination of quickly evolving pathogenic viruses in an adjustable, fast, and safe manner. Relying on MRI for visualization, the presented approach could be considered in the future to map ligand-receptor binding events in deep tissues, which are not accessible to luminescence-based imaging.

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Section: Resultsmentioning

confidence: 69%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

See 1 more Smart Citation

Genetically Engineered MRI-Trackable Extracellular Vesicles as SARS-CoV-2 Mimetics for Mapping ACE2 Binding In Vivo

et al. 2022

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“…The lung-derived exosomes enhanced the RBD uptake by APC, which can improve the effectivity of this vaccine candidate in mice. On the other hand, this vaccine candidate reduced severe pneumonia and inflammatory infiltrates in hamsters [ 133 ]. Popowski et al (2022) also revealed that lung-derived extracellular vesicles (Lung-Exo) were superior cargo for mRNA and protein vaccines.…”

Section: Msc-free Therapy For Sars-cov-2mentioning

confidence: 99%

Potential Cell-Based and Cell-Free Therapy for Patients with COVID-19

Tan

Alfarafisa

Septiani

et al. 2022

Cells

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Since it was first reported, the novel coronavirus disease 2019 (COVID-19) remains an unresolved puzzle for biomedical researchers in different fields. Various treatments, drugs, and interventions were explored as treatments for COVID. Nevertheless, there are no standard and effective therapeutic measures. Meanwhile, mesenchymal stem cell (MSC) therapy offers a new approach with minimal side effects. MSCs and MSC-based products possess several biological properties that potentially alleviate COVID-19 symptoms. Generally, there are three classifications of stem cell therapy: cell-based therapy, tissue engineering, and cell-free therapy. This review discusses the MSC-based and cell-free therapies for patients with COVID-19, their potential mechanisms of action, and clinical trials related to these therapies. Cell-based therapies involve the direct use and injection of MSCs into the target tissue or organ. On the other hand, cell-free therapy uses secreted products from cells as the primary material. Cell-free therapy materials can comprise cell secretomes and extracellular vesicles. Each therapeutic approach possesses different benefits and various risks. A better understanding of MSC-based and cell-free therapies is essential for supporting the development of safe and effective COVID-19 therapy.

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“…Moreover, RBD is immunodominant among spike subunits as previously reported [8][9] . Such tailorable RBD-functionalized virus-like particle could also facilitate study of the immune activation caused by various numbers and distribution patterns of RBD.Recent SARS-CoV-2 vaccine studies have mainly focused on study of excellent immunodominance (i.e., enhanced B-cell response and promising longer-lasting protective immunity) initiated by homologous or heterologous polyvalent RBD vaccines compared to monomeric RBD immunogens [8][9][10][11][12][13][14] . However, few studies have investigated the virus-cell interaction based on viral immunogens with specific arranged patterns, which might facilitate the understanding of viral infection and immune responses 15 .…”

mentioning

confidence: 99%

Viral infection and immunity view of SARS-CoV-2 using RBD-assembled DNA Soccer-ball Framework

Zhang

Chen

et al. 2022

Preprint

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Elevated understanding of the viral infection process contributes to development of neutralizing agents and vaccine to combat infectious diseases. Although crystal structure of single SARS-CoV-2 spike/RBD and host receptor ACE2 is known, the viral attachment and immune response initiated by numbers and distribution patterns of natural spikes on SARS-CoV-2 are still obscure. Leveraging a ~74 nm DNA soccer-ball framework (DSF), we developed an aptamer-guided SARS-CoV-2 RBD precisely assembly strategy, thereby exploring the viral infection and immune response in specific numbers and distributions of RBDs. Thirty evenly distributed RBDs on DSF could achieve sufficient binding affinity against host cell (Kd of 122.2 pM), whereas 60 evenly distributed RBDs on DSF could bind to host cell rapidly (Ka of 0.845 min-1). While RBDs in centralized manner compared to evenly distribution facilitated higher and faster binding to host. Moreover, evenly distributed 20 RBDs on DSF achieved up to 88% immunity elicitation of macrophage cells. Overall, this strategy provides a prospective direction for the assembly of virus-like particles based on DNA origami, thereby facilitating understanding of viral infection and efficient vaccine design.

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Exosomes decorated with a recombinant SARS-CoV-2 receptor-binding domain as an inhalable COVID-19 vaccine

Abstract: March 2021 Methodology Sample preparationCells were washed with MACS flow buffer (Miltenyi Biotec, Bergisch Gladbach, Germany) and permeabilized with BD Cytofix/ Cytoperm (BD Biosciences, San Jose, CA, USA) prior to incubation with antibodies against CD86-APC (565479; BD Biosciences,

Cited by 168 publications

References 63 publications

Genetically Engineered MRI-Trackable Extracellular Vesicles as SARS-CoV-2 Mimetics for Mapping ACE2 Binding In Vivo

Genetically Engineered MRI-Trackable Extracellular Vesicles as SARS-CoV-2 Mimetics for Mapping ACE2 Binding In Vivo

Potential Cell-Based and Cell-Free Therapy for Patients with COVID-19

Viral infection and immunity view of SARS-CoV-2 using RBD-assembled DNA Soccer-ball Framework

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