scholarly journals Dendritic cell targeting virus-like particle delivers mRNA for in vivo immunization

2021 ◽  
Author(s):  
Di Yin ◽  
Sikai Ling ◽  
Xiaolong Tian ◽  
Yang Li ◽  
Zhijue Xu ◽  
...  
Keyword(s):  
Sindbis Virus ◽  
Cytotoxic T Cell ◽  
Cell Immunity ◽  
Dc Vaccine ◽  
Virus Like Particle ◽  
Infection Models ◽  
Specific Igg ◽  
Hsv 1

Abstract mRNA vaccine was approved clinically in 2020. Future development includes delivering mRNA to dendritic cells (DCs) specifically to improve effectiveness and avoid off-target cytotoxicity. Here, we developed virus-like particles (VLPs) as a DC tropic mRNA vaccine vector and showed the prophylactic effects in both SARS-CoV-2 and HSV-1 infection models. The VLP mRNA vaccine elicited strong cytotoxic T cell immunity and durable antibody response with the spike-specific antibodies that lasted for more than 9 months. Importantly, we were able to target mRNA to DCs by pseudotyping VLP with engineered Sindbis virus glycoprotein and found the DC-targeting mRNA vaccine significantly enhanced the titer of antigen-specific IgG, protecting the hACE-2 mice from SARS-CoV-2 infection. Additionally, we showed DC-targeted mRNA vaccine also protected mice from HSV-1 infection when co-delivering the gB and gD mRNA. Thus, the VLP may serve as an in situ DC vaccine and accelerate the further development of mRNA vaccines.

In vivolocalization of antibodies raised againstEimeria maximawall forming bodies during sexual intracellular development

Parasitology ◽  
2014 ◽  
Vol 141 (13) ◽  
pp. 1726-1735 ◽  
Author(s):  
SONJA FRÖLICH ◽  
ANNISHA SHAHPAREE ◽  
VALERIE C. WASINGER ◽  
MICHAEL WALLACH
Keyword(s):  
Intestinal Lumen ◽  
Igg Antibodies ◽  
Human Pathogens ◽  
Apicomplexan Parasites ◽  
Eimeria Maxima ◽  
Specific Igg ◽  
Cytoplasmic Type ◽  
Specific Igg Antibodies

SUMMARYApicomplexan parasites cause devastating diseases in humans and livestock. Previously we demonstrated that antibodies targeting transmissible forms of the apicomplexan parasite,Eimeria, are effective at reducing parasite shedding thus preventing the transmission of the disease. However, the mechanisms responsible have not been fully defined. Moreover, there is no direct evidence that the parasite-specific IgG antibodies can reach the parasite developing in the enterocytes of the infected chicken host. This study summarizes our efforts using host immunity, parasite proteomics and 3D microscopy to provide a step forward in our understanding of how this immune response works.Eimeria maximais an important pathogen of poultry and used as a surrogate for a number of human pathogens includingToxoplasmaandPlasmodium. Our studies demonstrate that immunization with the purified wall forming bodies (WFBs) results in a production of parasite-specific IgG antibodies, which have the ability to reachin situgametocytes in the intestinal lumen and permeate the enterocyte/parasite membranes in order to bind to the cytoplasmic Type 1 and Type 2 WFBs. This raises the intriguing possibility that via this process antibodies block the development ofEimeria maxima in vivo.

scholarly journals Immune Escape of Tumors in Vivo by Expression of Cellular Flice-Inhibitory Protein

1999 ◽  
Vol 190 (7) ◽  
pp. 1033-1038 ◽  
Author(s):  
Jan Paul Medema ◽  
Joan de Jong ◽  
Thorbald van Hall ◽  
Cornelis J.M. Melief ◽  
Rienk Offringa
Keyword(s):  
T Cell ◽  
Immune Escape ◽  
Cytotoxic T Cell ◽  
Tumor Control ◽  
Tumor Escape ◽  
Inhibitory Protein ◽  
Cell Immunity ◽  
Induced Apoptosis

The antiapoptotic protein cellular FLICE (Fas-associated death domain–like IL-1β–converting enzyme) inhibitory protein (cFLIP) protects cells from CD95(APO-1/Fas)-induced apoptosis in vitro and was found to be overexpressed in human melanomas. However, cytotoxic T cell–induced apoptosis, which is critically involved in tumor control in vivo, is not inhibited by cFLIP in vitro, as only CD95- and not perforin-dependent lysis is affected. This calls into question whether cFLIP is sufficient to allow escape from T cell–dependent immunity. Using two murine tumors, we directly demonstrate that cFLIP does result in escape from T cell immunity in vivo. Moreover, tumor cells are selected in vivo for elevated cFLIP expression. Therefore, our data indicate that CD95-dependent apoptosis constitutes a more prominent mechanism for tumor clearance than has so far been anticipated and that blockade of this pathway can result in tumor escape even when the perforin pathway is operational.

scholarly journals Semiconducting polymer nano-PROTACs for activatable photo-immunometabolic cancer therapy

2021 ◽  
Vol 12 (1) ◽  
Author(s):  
Chi Zhang ◽  
Ziling Zeng ◽  
Dong Cui ◽  
Shasha He ◽  
Yuyan Jiang ◽  
...  
Keyword(s):  
Cancer Therapy ◽  
Protein Degradation ◽  
Protein Homeostasis ◽  
Semiconducting Polymer ◽  
Cell Immunity ◽  
Tumor Immunogenicity ◽  
Tumor Growth And Metastasis ◽  
Target Side

AbstractImmunometabolic intervention has been applied to treat cancer via inhibition of certain enzymes associated with intratumoral metabolism. However, small-molecule inhibitors and genetic modification often suffer from insufficiency and off-target side effects. Proteolysis targeting chimeras (PROTACs) provide an alternative way to modulate protein homeostasis for cancer therapy; however, the always-on bioactivity of existing PROTACs potentially leads to uncontrollable protein degradation at non-target sites, limiting their in vivo therapeutic efficacy. We herein report a semiconducting polymer nano-PROTAC (SPNpro) with phototherapeutic and activatable protein degradation abilities for photo-immunometabolic cancer therapy. SPNpro can remotely generate singlet oxygen (1O2) under NIR photoirradiation to eradicate tumor cells and induce immunogenic cell death (ICD) to enhance tumor immunogenicity. Moreover, the PROTAC function of SPNpro is specifically activated by a cancer biomarker (cathepsin B) to trigger targeted proteolysis of immunosuppressive indoleamine 2,3-dioxygenase (IDO) in the tumor of living mice. The persistent IDO degradation blocks tryptophan (Trp)-catabolism program and promotes the activation of effector T cells. Such a SPNpro-mediated in-situ immunometabolic intervention synergizes immunogenic phototherapy to boost the antitumor T-cell immunity, effectively inhibiting tumor growth and metastasis. Thus, this study provides a polymer platform to advance PROTAC in cancer therapy.

Depression of afferent arc of the in vivo cytotoxic T-Cell immunity by bacterial lipopolysaccharides

1985 ◽  
Vol 95 (2) ◽  
pp. 330-339 ◽  
Author(s):  
Kenji Mizoguchi ◽  
Izumi Nakashima ◽  
Yoshinori Hasegawa ◽  
Ken-ichi Isobe ◽  
Nobuo Kato ◽  
...  
Keyword(s):  
T Cell ◽  
T Cell Immunity ◽  
Cytotoxic T Cell ◽  
Cell Immunity ◽  
Bacterial Lipopolysaccharides

In vitro and in vivo polysaccharides assembly: ultrastructural and cytochemical study of growing plant cell wall components.

1978 ◽  
Vol 36 (2) ◽  
pp. 434-435
Author(s):  
D. Reis ◽  
B. Vian ◽  
J. C. Roland
Keyword(s):  
Cell Wall ◽  
Self Assembly ◽  
Plant Cell Wall ◽  
Higher Plants ◽  
Three Dimensional ◽  
Cytochemical Study ◽  
Wall Components

Wall morphogenesis in higher plants is a problem still open to controversy. Until now the possibility of a transmembrane control and the involvement of microtubules were mostly envisaged. Self-assembly processes have been observed in the case of walls of Chlamydomonas and bacteria. Spontaneous gelling interactions between xanthan and galactomannan from Ceratonia have been analyzed very recently. The present work provides indications that some processes of spontaneous aggregation could occur in higher plants during the formation and expansion of cell wall.Observations were performed on hypocotyl of mung bean (Phaseolus aureus) for which growth characteristics and wall composition have been previously defined.In situ, the walls of actively growing cells (primary walls) show an ordered three-dimensional organization (fig. 1). The wall is typically polylamellate with multifibrillar layers alternately transverse and longitudinal. Between these layers intermediate strata exist in which the orientation of microfibrils progressively rotates. Thus a progressive change in the morphogenetic activity occurs.

Three-Dimensional Subcellular Organization of Hepatocytes in Intact Liver: Simultaneous Visualization of Cytoskeletal and Membrane Markers by Confocal Microscopy

1996 ◽  
Vol 54 ◽  
pp. 288-289
Author(s):  
Greg V. Martin ◽  
Ann L. Hubbard
Keyword(s):  
Three Dimensional ◽  
Integral Membrane Proteins ◽  
Polarized Secretion ◽  
Microscope Images ◽  
Computer Aided ◽  
Intracellular Organelles ◽  
Cytoskeletal Elements ◽  
Simultaneous Visualization

The microtubule (MT) cytoskeleton is necessary for many of the polarized functions of hepatocytes. Among the functions dependent on the MT-based cytoskeleton are polarized secretion of proteins, delivery of endocytosed material to lysosomes, and transcytosis of integral plasma membrane (PM) proteins. Although microtubules have been shown to be crucial to the establishment and maintenance of functional and structural polarization in the hepatocyte, little is known about the architecture of the hepatocyte MT cytoskeleton in vivo, particularly with regard to its relationship to PM domains and membranous organelles. Using an in situ extraction technique that preserves both microtubules and cellular membranes, we have developed a protocol for immunofluorescent co-localization of cytoskeletal elements and integral membrane proteins within 20 µm cryosections of fixed rat liver. Computer-aided 3D reconstruction of multi-spectral confocal microscope images was used to visualize the spatial relationships among the MT cytoskeleton, PM domains and intracellular organelles.

Evaluation of Structure-Controlled Silk Fibroin Coatings for Orthopedic Infection and In-Situ Osteogenesis: In Vitro and In Vivo

2020 ◽  
Author(s):  
Wenhao Zhou ◽  
Teng Zhang ◽  
Jianglong Yan ◽  
QiYao Li ◽  
Panpan Xiong ◽  
...  
Keyword(s):  
Silk Fibroin ◽  
Orthopedic Infection

scholarly journals Ferromagnetic soft catheter robots for minimally invasive bioprinting

2021 ◽  
Vol 12 (1) ◽  
Author(s):  
Cheng Zhou ◽  
Youzhou Yang ◽  
Jiaxin Wang ◽  
Qingyang Wu ◽  
Zhuozhi Gu ◽  
...  
Keyword(s):  
Minimally Invasive ◽  
The Body ◽  
Magnetic Actuation ◽  
Internal Organs ◽  
Planar Surfaces ◽  
Reinforced Polymer ◽  
Direct Fabrication ◽  
Digitally Controlled

AbstractIn vivo bioprinting has recently emerged as a direct fabrication technique to create artificial tissues and medical devices on target sites within the body, enabling advanced clinical strategies. However, existing in vivo bioprinting methods are often limited to applications near the skin or require open surgery for printing on internal organs. Here, we report a ferromagnetic soft catheter robot (FSCR) system capable of in situ computer-controlled bioprinting in a minimally invasive manner based on magnetic actuation. The FSCR is designed by dispersing ferromagnetic particles in a fiber-reinforced polymer matrix. This design results in stable ink extrusion and allows for printing various materials with different rheological properties and functionalities. A superimposed magnetic field drives the FSCR to achieve digitally controlled printing with high accuracy. We demonstrate printing multiple patterns on planar surfaces, and considering the non-planar surface of natural organs, we then develop an in situ printing strategy for curved surfaces and demonstrate minimally invasive in vivo bioprinting of hydrogels in a rat model. Our catheter robot will permit intelligent and minimally invasive bio-fabrication.

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