Lipid-Mediated Cell Surface Engineering

Patel, Jaina; Vartabedian, Vincent F.; Selvaraj, Periasamy

doi:10.1016/b978-1-4557-3146-6.00006-4

Cited by 3 publications

(4 citation statements)

References 84 publications

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“…The GPI-anchor consists of two fatty acid chains that allow for insertion of the GPI-ISMs into the lipid bilayer by protein transfer (27–29). Phosphatidylinositol-specific phospholipase C (PI-PLC) cleaves the GPI-anchor from the ISM leaving the remaining protein domain intact (30).…”

Section: Resultsmentioning

confidence: 99%

Protein transfer-mediated surface engineering to adjuvantate virus-like nanoparticles for enhanced anti-viral immune responses

Patel

Kim

Vartabedian

et al. 2015

Nanomedicine: Nanotechnology, Biology and Medicine

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Recombinant virus-like nanoparticles (VLPs) are a promising nanoparticle platform to develop safe vaccines for many viruses. Herein, we describe a novel and rapid protein transfer process to enhance the potency of enveloped VLPs by decorating influenza VLPs with exogenously added glycosylphosphatidylinositol-anchored immunostimulatory molecules (GPI-ISMs). With protein transfer, the level of GPI-ISM incorporation onto VLPs is controllable by varying incubation time and concentration of GPI-ISMs added. ISM incorporation was dependent upon the presence of a GPI-anchor and incorporated proteins were stable and functional for at least 4 weeks when stored at 4°C. Vaccinating mice with GPI-granulocyte macrophage colony-stimulating factor (GM-CSF)-incorporated-VLPs induced stronger antibody responses and better protection against a heterologous influenza virus challenge than unmodified VLPs. Thus, VLPs can be enriched with ISMs by protein transfer to increase the potency and breadth of the immune response, which has implications in developing effective nanoparticle-based vaccines against a broad spectrum of enveloped viruses.

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Section: Resultsmentioning

confidence: 99%

Protein transfer-mediated surface engineering to adjuvantate virus-like nanoparticles for enhanced anti-viral immune responses

Patel

Kim

Vartabedian

et al. 2015

Nanomedicine: Nanotechnology, Biology and Medicine

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“…In order to test whether the PMVs can be used as a scaffold to deliver TAAs by protein transfer we aimed to deliver the breast cancer antigen, HER-2. However, protein transfer-mediated modification of PMVs requires proteins to have a covalently attached lipid tail which spontaneously anchors the protein into the lipid bilayer through a lipid-lipid interaction (14, 18, 21). Therefore, we converted the transmembrane HER-2 antigen into GPI-anchored-HER-2 by attaching the GPI-anchor signal sequence DNA from CD59, a GPI-anchored protein, to the extracellular DNA domain of HER-2 in a pUB6 blast vector (Figure 2A).…”

Section: Resultsmentioning

confidence: 99%

“…This method results in the formation of vesicles from plasma membranes; thus PMVs contain lipid bilayers, making them amenable to modification by protein transfer. Protein transfer uses glycosylphosphatidylinositol-anchored immunostimulatory molecules (GPI-ISMs) to modify cell or membrane surfaces in a simple, rapid process whereby cells or membranes are incubated with purified GPI-ISMs for 2–4 hours (16, 17, 19–21). Incubation results in the spontaneous incorporation of the GPI-ISMs onto cell membranes via the GPI-anchor in a concentration, time and temperature-dependent manner (16, 17, 19) and expression of incorporated GPI-ISMs on PMVs is not affected even after storage of the protein transferred vesicles (19).…”

Section: Introductionmentioning

confidence: 99%

Plasma membrane vesicles decorated with glycolipid-anchored antigens and adjuvants via protein transfer as an antigen delivery platform for inhibition of tumor growth

et al. 2016

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Antigen delivered within particulate materials leads to enhanced antigen-specific immunity compared to soluble administration of antigen. However, current delivery approaches for antigen encapsulated in synthetic particulate materials are limited by the complexity of particle production that affects stability and immunogenicity of the antigen. Herein, we describe a protein delivery system that utilizes plasma membrane vesicles (PMVs) derived from biological materials such as cultured cells or isolated tissues and a simple protein transfer technology. We show that these particulate PMVs can be easily modified within 4 h by a protein transfer process to stably incorporate a glycosylphosphatidylinositol (GPI)-anchored form of the breast cancer antigen HER-2 onto the PMV surface. Immunization of mice with GPI-HER-2-modified-PMVs induced strong HER-2-specific antibody responses and protection from tumor challenge in two different breast cancer models. Further incorporation of the immunostimulatory molecules IL-12 and B7-1 onto the PMVs by protein transfer enhanced tumor protection and induced beneficial Th1 and Th2-type HER-2-specific immune responses. Since protein antigens can be easily converted to GPI-anchored forms, these results demonstrate that isolated plasma membrane vesicles can be modified with desired antigens along with immunostimulatory molecules by protein transfer and used as a vaccine delivery vehicle to elicit potent antigen-specific immunity.

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“…These are successfully used to deliver multiple antigens as vaccines [58,59]. Influenza VLPs are lipid enveloped nanoparticles and therefore amenable to the protein transfer mediated incorporation of GPI-anchored antigens and cytokines [12,40,60]. Protein transfer allows us to incorporate multiple GPI-anchored antigens and adjuvants into lipid enveloped VLPs.…”

Section: Discussionmentioning

confidence: 99%

Influenza Virus-like Particle-Based Hybrid Vaccine Containing RBD Induces Immunity against Influenza and SARS-CoV-2 Viruses

et al. 2022

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Several approaches have produced an effective vaccine against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Since millions of people are exposed to influenza virus and SARS-CoV-2, it is of great interest to develop a two-in-one vaccine that will be able to protect against infection of both viruses. We have developed a hybrid vaccine for SARS-CoV-2 and influenza viruses using influenza virus-like particles (VLP) incorporated by protein transfer with glycosylphosphatidylinositol (GPI)-anchored SARS-CoV-2 RBD fused to GM-CSF as an adjuvant. GPI-RBD-GM-CSF fusion protein was expressed in CHO-S cells, purified and incorporated onto influenza VLPs to develop the hybrid vaccine. Our results show that the hybrid vaccine induced a strong antibody response and protected mice from both influenza virus and mouse-adapted SARS-CoV-2 challenges, with vaccinated mice having significantly lower lung viral titers compared to naive mice. These results suggest that a hybrid vaccine strategy is a promising approach for developing multivalent vaccines to prevent influenza A and SARS-CoV-2 infections.

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Lipid-Mediated Cell Surface Engineering

Cited by 3 publications

References 84 publications

Protein transfer-mediated surface engineering to adjuvantate virus-like nanoparticles for enhanced anti-viral immune responses

Protein transfer-mediated surface engineering to adjuvantate virus-like nanoparticles for enhanced anti-viral immune responses

Plasma membrane vesicles decorated with glycolipid-anchored antigens and adjuvants via protein transfer as an antigen delivery platform for inhibition of tumor growth

Influenza Virus-like Particle-Based Hybrid Vaccine Containing RBD Induces Immunity against Influenza and SARS-CoV-2 Viruses

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