scholarly journals Successful attenuation of humoral immunity to viral capsid and transgenic protein following AAV-mediated gene transfer with a non-depleting CD4 antibody and cyclosporine

Gene Therapy ◽  
2011 ◽  
Vol 19 (1) ◽  
pp. 78-85 ◽  
Author(s):  
J H McIntosh ◽  
M Cochrane ◽  
S Cobbold ◽  
H Waldmann ◽  
S A Nathwani ◽  
...  
Keyword(s):  
Gene Transfer ◽  
Humoral Immunity ◽  
Viral Capsid ◽  
Transgenic Protein

scholarly journals Prevalence and pharmacological modulation of humoral immunity to AAV vectors in gene transfer to synovial tissue

Gene Therapy ◽  
2012 ◽  
Vol 20 (4) ◽  
pp. 417-424 ◽  
Author(s):  
F Mingozzi ◽  
Y Chen ◽  
S C Edmonson ◽  
S Zhou ◽  
R M Thurlings ◽  
...  
Keyword(s):  
Gene Transfer ◽  
Synovial Tissue ◽  
Humoral Immunity ◽  
Pharmacological Modulation

scholarly journals Ovine Adenovirus Vectors Overcome Preexisting Humoral Immunity against Human Adenoviruses In Vivo

1999 ◽  
Vol 73 (8) ◽  
pp. 6930-6936 ◽  
Author(s):  
Christian Hofmann ◽  
Peter Löser ◽  
Günter Cichon ◽  
Wolfgang Arnold ◽  
Gerald W. Both ◽  
...  
Keyword(s):  
Gene Transfer ◽  
Humoral Immunity ◽  
Functional Expression ◽  
Immunodeficient Mice ◽  
Human Adenoviruses ◽  
Rous Sarcoma ◽  
Efficient Gene ◽  
Human Sera ◽  
Adenovirus Vectors

ABSTRACT Recombinant human adenoviruses (hAd) have become widely used as tools to achieve efficient gene transfer. However, successful application of hAd-derived vectors in clinical trials is limited due to immunological and potential safety problems inherent in their human origin. In this study, we describe a recombinant ovine adenovirus (OAV) as an alternative vector for gene transfer in vivo. In contrast to an hAd vector, the OAV vector was not neutralized by human sera. An OAV vector which contained the cDNA of the human α1-antitrypsin (hAAT) gene linked to the Rous sarcoma virus promoter was generated and administered systemically to mice. The level and duration of hAAT gene expression was similar to that achieved with an hAd counterpart in both immunocompetent and immunodeficient mice. However, the tissue distribution of the OAV vector differed from that observed for hAd vectors in that the liver was not the dominant target. Significantly, we demonstrated efficient gene transfer with the OAV vector into mice immunized with hAd vectors and vice versa. We also confirm that the immune response to a transgene product can prevent its functional expression following sequential application of a vector. Our results suggest a possible solution to endemic humoral immunity against currently used hAd vectors and should therefore have an impact on the design of improved gene therapy protocols utilizing adenovirus vectors.

scholarly journals Enhanced liver gene transfer and evasion of preexisting humoral immunity with exosome-enveloped AAV vectors

2017 ◽  
Vol 1 (23) ◽  
pp. 2019-2031 ◽  
Author(s):  
Amine Meliani ◽  
Florence Boisgerault ◽  
Zachary Fitzpatrick ◽  
Solenne Marmier ◽  
Christian Leborgne ◽  
...  
Keyword(s):  
Gene Transfer ◽  
Humoral Immunity ◽  
Hemophilia B ◽  
Key Points ◽  
Liver Gene

Key Points Enveloped AAV vectors are able to transduce the liver highly efficiently, driving superior correction of hemophilia B in mice. Enveloped AAVs are less susceptible to antibody-mediated neutralization, allowing for liver transduction in preimmunized animals.

scholarly journals Immune Response to Recombinant Capsid Proteins of Adenovirus in Humans: Antifiber and Anti-Penton Base Antibodies Have a Synergistic Effect on Neutralizing Activity

1998 ◽  
Vol 72 (3) ◽  
pp. 2388-2397 ◽  
Author(s):  
Hanne Gahéry-Ségard ◽  
Françoise Farace ◽  
Dominique Godfrin ◽  
Jesintha Gaston ◽  
Renée Lengagne ◽  
...  
Keyword(s):  
Gene Therapy ◽  
Immune Response ◽  
Gene Transfer ◽  
Synergistic Effect ◽  
Humoral Response ◽  
Viral Capsid ◽  
Penton Base ◽  
Strong Immune Response ◽  
Neutralizing Activity ◽  
Humoral Immune

ABSTRACT Replication-deficient adenovirus used in humans for gene therapy induces a strong immune response to the vector, resulting in transient recombinant protein expression and the blocking of gene transfer upon a second administration. Therefore, in this study we examined in detail the capsid-specific humoral immune response in sera of patients with lung cancer who had been given one dose of a replication-defective adenovirus. We analyzed the immune response to the three major components of the viral capsid, hexon (Hx), penton base (Pb), and fiber (Fi). A longitudinal study of the humoral response assayed on adenovirus particle-coated enzyme-linked immunosorbent assay plates showed that patients had preexisting immunity to adenovirus prior to the administration of adenovirus–β-gal. The level of the response increased in three patients after adenovirus administration and remained at a maximum after three months. One patient had a strong immune response to adenovirus prior to treatment, and this response was unaffected by adenovirus administration. Sera collected from the patients were assayed for recognition of each individual viral capsid protein to determine more precisely the molecular basis of the humoral immune response. Clear differences existed in the humoral response to the three major components of the viral capsid in serum from humans. Sequential appearance of these antibodies was observed: anti-Fi antibodies appeared first, followed by anti-Pb antibodies and then by anti-Hx antibodies. Moreover, anti-Fi antibodies preferentially recognized the native trimeric form of Fi protein, suggesting that they recognized conformational epitopes. Our results showed that sera with no neutralizing activity contained only anti-Fi antibodies. In contrast, neutralizing activity was only obtained with sera containing anti-Fi and anti-Pb antibodies. More importantly, we showed that anti-native Fi and anti-Pb antibodies had a synergistic effect on neutralization. The application of these conclusions to human gene therapy with recombinant adenovirus should lead to the development of strategies to overcome the formation of such neutralization antibodies, which have been shown to limit the efficacy of gene transfer in humans.

scholarly journals Pharmacological Modulation of Humoral Immunity in a Nonhuman Primate Model of AAV Gene Transfer for Hemophilia B

2012 ◽  
Vol 20 (7) ◽  
pp. 1410-1416 ◽  
Author(s):  
Federico Mingozzi ◽  
Yifeng Chen ◽  
Samuel L Murphy ◽  
Shyrie C Edmonson ◽  
Alex Tai ◽  
...  
Keyword(s):  
Gene Transfer ◽  
Humoral Immunity ◽  
Nonhuman Primate ◽  
Hemophilia B ◽  
Nonhuman Primate Model ◽  
Primate Model ◽  
Pharmacological Modulation

Phagocytosis of opsonized red blood cells by hepatocytes after gene transfer of chimeric Fc γR III Aα and γcDNA

2001 ◽  
Vol 120 (5) ◽  
pp. A356-A357
Author(s):  
M FURUKAWA ◽  
Y MAGAMI ◽  
D NAKAYAMA ◽  
F MORIYASU ◽  
J PARK ◽  
...  
Keyword(s):  
Gene Transfer ◽  
Red Blood Cells ◽  
Blood Cells

1860: Generation of Fluorescent Sperm by Use of in VIVO Gene Transfer to Hamster Testes

2007 ◽  
Vol 177 (4S) ◽  
pp. 617-618
Author(s):  
Hiraki Kubota ◽  
Kevin Coward ◽  
Olivia Hibbitt ◽  
Nilendran Prathalingam ◽  
William Holt ◽  
...  
Keyword(s):  
Gene Transfer ◽  
In Vivo Gene Transfer

1509: Adeno-Associated Virus-Mediated Human IL-10 Gene Transfer Suppresses the Development of Experimental Autoimmune Orchitis

2005 ◽  
Vol 173 (4S) ◽  
pp. 409-409
Author(s):  
Masami Watanabe ◽  
Atsushi Nagai ◽  
Norihiro Kusumi ◽  
Yasutomo Nasu ◽  
Hiromi Kumon ◽  
...  
Keyword(s):  
Gene Transfer ◽  
Adeno Associated Virus ◽  
Autoimmune Orchitis ◽  
Experimental Autoimmune
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