scholarly journals Lethal Hepatitis After Gene Transfer of IL-4 in the Liver Is Independent of Immune Responses and Dependent on Apoptosis of Hepatocytes: A Rodent Model of IL-4-Induced Hepatitis

2001 ◽  
Vol 166 (8) ◽  
pp. 5225-5235 ◽  
Author(s):  
Cécile Guillot ◽  
Hélène Coathalem ◽  
Jérôme Chetritt ◽  
Anne David ◽  
Pedro Lowenstein ◽  
...  
Keyword(s):  
Gene Transfer ◽  
Immune Responses ◽  
Rodent Model

scholarly journals Retrograde Transgene Expression via Neuron-Specific Lentiviral Vector Depends on Both Species and Input Projections

Viruses ◽  
2021 ◽  
Vol 13 (7) ◽  
pp. 1387
Author(s):  
Yukiko Otsuka ◽  
Hitomi Tsuge ◽  
Shiori Uezono ◽  
Soshi Tanabe ◽  
Maki Fujiwara ◽  
...  
Keyword(s):  
Gene Transfer ◽  
Immune Responses ◽  
Envelope Glycoprotein ◽  
Transgene Expression ◽  
Histological Analysis ◽  
Lentiviral Vector ◽  
Cortical Input ◽  
Input System ◽  
Vesicular Stomatitis ◽  
Retrograde Gene Transfer

For achieving retrograde gene transfer, we have so far developed two types of lentiviral vectors pseudotyped with fusion envelope glycoprotein, termed HiRet vector and NeuRet vector, consisting of distinct combinations of rabies virus and vesicular stomatitis virus glycoproteins. In the present study, we compared the patterns of retrograde transgene expression for the HiRet vs. NeuRet vectors by testing the cortical input system. These vectors were injected into the motor cortex in rats, marmosets, and macaques, and the distributions of retrograde labels were investigated in the cortex and thalamus. Our histological analysis revealed that the NeuRet vector generally exhibits a higher efficiency of retrograde gene transfer than the HiRet vector, though its capacity of retrograde transgene expression in the macaque brain is unexpectedly low, especially in terms of the intracortical connections, as compared to the rat and marmoset brains. It was also demonstrated that the NeuRet but not the HiRet vector displays sufficiently high neuron specificity and causes no marked inflammatory/immune responses at the vector injection sites in the primate (marmoset and macaque) brains. The present results indicate that the retrograde transgene efficiency of the NeuRet vector varies depending not only on the species but also on the input projections.

scholarly journals Major role of local immune responses in antibody formation to factor IX in AAV gene transfer

Gene Therapy ◽  
2005 ◽  
Vol 12 (19) ◽  
pp. 1453-1464 ◽  
Author(s):  
L Wang ◽  
O Cao ◽  
B Swalm ◽  
E Dobrzynski ◽  
F Mingozzi ◽  
...  
Keyword(s):  
Gene Transfer ◽  
Immune Responses ◽  
Antibody Formation ◽  
Factor Ix

The effect of changes in nutrient demand on gastrointestinal parasitism in lactating rats

2005 ◽  
Vol 2005 ◽  
pp. 12-12 ◽  
Author(s):  
H. N. Normanton ◽  
J. G. M. Houdijk ◽  
N. S. Jessop ◽  
D. P. Knox ◽  
I. Kyriazakis
Keyword(s):  
Food Intake ◽  
Immune Responses ◽  
Worm Burden ◽  
Nutrient Supply ◽  
Rodent Model ◽  
Nutrient Demand ◽  
Per Se ◽  
Immunological Changes ◽  
Gastrointestinal Parasitism ◽  
Protein Supply

A recent study carried out by Houdijk et al (2005), used a rodent model to assess whether a reduction in protein scarcity during lactation resulted in a reduced degree of parasitism. Feeding high protein foods resulted in a reduced worm burden, but was confounded with increased food intake per se. Therefore, effects observed on parasitism may not necessarily have been associated with an increased protein supply, but with changes in the gut environment due to the increased food intake. Before this model can be used to assess the underlying immune responses, further work is needed to verify that the effects observed are indeed related to changes in nutrient supply. This experiment aimed to provide further evidence on the nutritional control of parasitism during lactation by manipulating nutrient demand. It was expected that the latter would not be associated with changes in food intake per se and results could therefore be used to exclude the influence of non-immunological changes in the gut environment as a contributing factor of reduced parasitism.

The induction of immune responses to murine malignant mesothelioma by IL-2 gene transfer

1997 ◽  
Vol 75 (4) ◽  
pp. 356-359 ◽  
Author(s):  
Clement C Leong ◽  
Julia V Marley ◽  
Suzanne Loh ◽  
Bruce WS Robinson ◽  
Michael J Garlepp
Keyword(s):  
Gene Transfer ◽  
Immune Responses ◽  
Malignant Mesothelioma

scholarly journals Adenovirus capsid-display of the retro-oriented human complement inhibitor DAF reduces Ad vector–triggered immune responses in vitro and in vivo

Blood ◽  
2010 ◽  
Vol 116 (10) ◽  
pp. 1669-1677 ◽  
Author(s):  
Sergey S. Seregin ◽  
Yasser A. Aldhamen ◽  
Daniel M. Appledorn ◽  
Zachary C. Hartman ◽  
Nathaniel J. Schuldt ◽  
...  
Keyword(s):  
Gene Transfer ◽  
Immune Responses ◽  
Cell Activation ◽  
Innate Immune ◽  
Complement Inhibitor ◽  
Human Complement ◽  
Endothelial Cell Activation ◽  
Capsid Display

Abstract Adenovirus (Ad) vectors are widely used in human clinical trials. However, at higher dosages, Ad vector–triggered innate toxicities remain a major obstacle to many applications. Ad interactions with the complement system significantly contribute to innate immune responses in several models of Ad-mediated gene transfer. We constructed a novel class of Ad vectors, genetically engineered to “capsid-display” native and retro-oriented versions of the human complement inhibitor decay-accelerating factor (DAF), as a fusion protein from the C-terminus of the Ad capsid protein IX. In contrast to conventional Ad vectors, DAF-displaying Ads dramatically minimized complement activation in vitro and complement-dependent immune responses in vivo. DAF-displaying Ads did not trigger thrombocytopenia, minimized endothelial cell activation, and had diminished inductions of proinflammatory cytokine and chemokine responses. The retro-oriented display of DAF facilitated the greatest improvements in vivo, with diminished activation of innate immune cells, such as dendritic and natural killer cells. In conclusion, Ad vectors can capsid-display proteins in a manner that not only retains the functionality of the displayed proteins but also potentially can be harnessed to improve the efficacy of this important gene transfer platform for numerous gene transfer applications.

scholarly journals The genome of self-complementary adeno-associated viral vectors increases Toll-like receptor 9–dependent innate immune responses in the liver

Blood ◽  
2011 ◽  
Vol 117 (24) ◽  
pp. 6459-6468 ◽  
Author(s):  
Ashley T. Martino ◽  
Masataka Suzuki ◽  
David M. Markusic ◽  
Irene Zolotukhin ◽  
Renee C. Ryals ◽  
...  
Keyword(s):  
Gene Transfer ◽  
Immune Responses ◽  
Viral Vectors ◽  
Killer Cell ◽  
Primary Response ◽  
Innate Immune ◽  
Adaptive Immune Responses ◽  
Adaptive Immune ◽  
Capsid Sequence ◽  
Inducible Protein

AbstractAlthough adeno-associated viral (AAV) vectors have been successfully used in hepatic gene transfer for treatment of hemophilia and other diseases in animals, adaptive immune responses blocked long-term transgene expression in patients on administration of single-stranded AAV serotype-2 vector. More efficient vectors have been developed using alternate capsids and self-complimentary (sc) genomes. This study investigated their effects on the innate immune profile on hepatic gene transfer to mice. A mild and transient up-regulation of myeloid differentiation primary response gene (88), TLR9, TNF-α, monocyte chemotactic protein-1, IFN-γ inducible protein-10, and IFN-α/β expression in the liver was found after single-stranded AAV vector administration, regardless of the capsid sequence. In contrast, scAAV vectors induced higher increases of these transcripts, upregulated additional proinflammatory genes, and increased circulating IL-6. Neutrophil, macrophage, and natural killer cell liver infiltrates were substantially higher on injection of scAAV. Some but not all of these responses were Kupffer cell dependent. Independent of the capsid or expression cassette, scAAV vectors induced dose-dependent innate responses by signaling through TLR9. Increased innate responses to scAAV correlated with stronger adaptive immune responses against capsid (but not against the transgene product). However, these could be blunted by transient inhibition of TLR9.

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