Photodynamic treatment of adenoviral vectors with visible light: an easy and convenient method for viral inactivation

Schagen, Frederik H.E.; Moor, Anne C.E.; Cheong, Siew Chiat; Cramer, Steve; Ormondt, H. van; Eb, A. J. Van Der; Dubbelman, T. M. A. R.; Hoeben, Rob C.

doi:10.1038/sj.gt.3300897

Cited by 54 publications

(27 citation statements)

References 31 publications

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“…MB inactivation of Ad was previously shown to reduce viral infectivity by at least 4 logs after illumination for 10 min (40). Prolonging the illumination period revealed that infectious particles could no longer be detected after 30 min of inactivation, as determined by the lack of cytopathological effect in human epithelial cells (HEp-2) cells, indicating that MB can inactivate Ad5 by at least 7 logs (data not shown).…”

Section: Inactivation Of Ad Stimulation Of Ad-specific T Cells By Usmentioning

confidence: 97%

“…In clinical practice, however, biosafety constraints require a validated inactivation procedure of the Ad used for T-cell stimulation in order to circumvent infusion of infectious or genetically modified virus into the patient. Our strategy has therefore focused on complete inactivation of purified wild-type virus by using the photosensitizer methylene blue (MB) and visible light (40). MB is already in use for routine treatment of fresh frozen plasma prior to infusion to inactivate viruses such as hepatitis C virus (33,35,42).…”

Section: Inactivation Of Ad Stimulation Of Ad-specific T Cells By Usmentioning

confidence: 99%

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Extensive Cross-Reactivity of CD4⁺Adenovirus-Specific T Cells: Implications for Immunotherapy and Gene Therapy

Heemskerk¹,

Veltrop-Duits²,

Vreeswijk³

et al. 2003

J Virol

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Section: Inactivation Of Ad Stimulation Of Ad-specific T Cells By Usmentioning

confidence: 97%

Section: Inactivation Of Ad Stimulation Of Ad-specific T Cells By Usmentioning

confidence: 99%

Extensive Cross-Reactivity of CD4⁺Adenovirus-Specific T Cells: Implications for Immunotherapy and Gene Therapy

Heemskerk¹,

Veltrop-Duits²,

Vreeswijk³

et al. 2003

J Virol

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“…CAVGFP had a physical particle (pp)-to-infectious-unit (IU) ratio of 3:1, while AdGFP had a pp/IU ratio of 10:1 (31). AdGFP, CAVGFP, and wild-type HAd serotypes were UV/psoralen inactivated postpurification as previously described (58,78). The nomenclature "CAV-2" and "HAd5" are used throughout the text instead of CAVGFP and AdGFP to denote that the assays were transgene independent.…”

Section: Methodsmentioning

confidence: 99%

Frequency, Proliferation, and Activation of Human Memory T Cells Induced by a Nonhuman Adenovirus

Perreau

Kremer

2005

J Virol

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Multiple human adenovirus (HAd) infections during childhood generate a memory T-cell (T M ) response, which is the primary defense against HAd-induced morbidity. This cellular memory creates a conundrum for the potential clinical use of HAd-derived vectors: vector-mediated gene transfer is efficient in immunologically naïve mammals but will be compromised by memory immunity when using vectors derived from ubiquitous human pathogens. The potential lack of cellular and humoral memory is one reason we developed vectors from canine adenovirus serotype 2 (CAV-2). Here, we assayed human peripheral blood mononuclear cells for a T M response that could be stimulated by CAV-2 virion and individual capsid proteins. We found that less than half of the donors harbored a proliferating T M response directed against the CAV-2 virion (versus >85% against HAd5) in spite of a conserved antigenic Adenoviridae epitope in the CAV-2 hexon. When CAV-2 induced proliferation, it was 2.3-to >10-fold lower than HAd5 depending on the assay. The primary proliferating cells appeared to be memory (CD45RO ؉ ) CD4 ؉ lymphocytes, differentiated into Th1 gamma interferon-producing cells, with a frequency that was up to 66-fold lower than that obtained for HAd5. We also compared CAV-2 to prototype HAd from five of the six human species and found that CAV-2-induced cellular proliferation was similar to that found with rare HAd serotypes. Individual CAV-2 capsid proteins also induced less proliferation than their HAd5 homologues. Our data suggest that CAV-2 vectors may be safer (i.e., less immunogenic) for gene transfer but are not without a theoretical risk in a subset of potential patients.One of the more salient characteristics of adaptive immunity is the generation of immunological memory. This phenomenon enhances protection from previously encountered pathogens and is the basis for global vaccination strategies of numerous infectious diseases. T-cell memory (T M ) is an evolving, dynamic process that maintains a minimum level of antigenspecific T cells that rely on a renewable population in the absence of stimuli (20,21,34,75). The extraordinary flexibility for T M antigen recognition (62) is due to the ability of major histocompatibility complex (MHC) class I and II alleles to accommodate sequence divergence. There are two major subsets of T M , CD4 ϩ and CD8 ϩ , although the former are considered more as helpers for CD8 ϩ T M -mediated lysis and CD4 ϩ

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“…7A). MB inactivation prohibits gene transcription (34), indicating that viral protein synthesis is not required, and that processing of input virions can be sufficient for presentation of T cell epitopes on HLA class II.…”

Section: Loading Of Hexon Peptide On Mhc Class II Moleculesmentioning

confidence: 99%

Adenovirus-Specific CD4+ T Cell Clones Recognizing Endogenous Antigen Inhibit Viral Replication In Vitro through Cognate Interaction

Heemskerk

Vreeswijk

Veltrop-Duits

et al. 2006

The Journal of Immunology

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Human adenovirus (HAdV) infection is a frequent and potentially severe complication following allogeneic stem cell transplantation in children. Because treatment with antiviral drugs is often ineffective, adoptive transfer of donor-derived HAdV-specific T cells able to control viral replication of HAdV of multiple serotypes may be an option for therapy. In healthy donors, predominantly HAdV-specific T cells expressing CD4 are detected. In this study, a preclinical in vitro model was used to measure the antiviral effect of HAdV-specific CD4+ T cells. CD4+ HAdV-specific T cell clones restricted by HLA class II molecules were generated and most of these clones recognized conserved peptides derived from the hexon protein. These cross-reactive T cell clones were able to control viral replication of multiple serotypes of HAdV in EBV-transformed B cells (B-LCL), melanoma cells (MJS) and primary bronchial epithelial cells through cognate interaction. The HAdV-specific CD4+ T cell clones were able to specifically lyse infected target cells using a perforin-dependent mechanism. Antigenic peptides were also presented to the CD4+ T cell clones when derived from endogenously produced hexon protein. Together, these results show that cross-reactive HAdV-specific CD4+ T cells can control replication of HAdV in vitro and provide a rationale for the use of HAdV-specific T cells in adoptive immunotherapy protocols for control of life-threatening HAdV-infections in immunocompromised patients.

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Photodynamic treatment of adenoviral vectors with visible light: an easy and convenient method for viral inactivation

Cited by 54 publications

References 31 publications

Extensive Cross-Reactivity of CD4⁺Adenovirus-Specific T Cells: Implications for Immunotherapy and Gene Therapy

Extensive Cross-Reactivity of CD4⁺Adenovirus-Specific T Cells: Implications for Immunotherapy and Gene Therapy

Frequency, Proliferation, and Activation of Human Memory T Cells Induced by a Nonhuman Adenovirus

Adenovirus-Specific CD4+ T Cell Clones Recognizing Endogenous Antigen Inhibit Viral Replication In Vitro through Cognate Interaction

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Photodynamic treatment of adenoviral vectors with visible light: an easy and convenient method for viral inactivation

Cited by 54 publications

References 31 publications

Extensive Cross-Reactivity of CD4+Adenovirus-Specific T Cells: Implications for Immunotherapy and Gene Therapy

Extensive Cross-Reactivity of CD4+Adenovirus-Specific T Cells: Implications for Immunotherapy and Gene Therapy

Frequency, Proliferation, and Activation of Human Memory T Cells Induced by a Nonhuman Adenovirus

Adenovirus-Specific CD4+ T Cell Clones Recognizing Endogenous Antigen Inhibit Viral Replication In Vitro through Cognate Interaction

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Extensive Cross-Reactivity of CD4⁺Adenovirus-Specific T Cells: Implications for Immunotherapy and Gene Therapy

Extensive Cross-Reactivity of CD4⁺Adenovirus-Specific T Cells: Implications for Immunotherapy and Gene Therapy