Ovine atadenovirus: a review of its biology, biosafety profile and application as a gene delivery vector

Both, Gerald W.

doi:10.1046/j.0818-9641.2004.01223.x

Cited by 27 publications

(22 citation statements)

References 52 publications

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“…An initial model was made by further binning projections by a factor of 2 (yielding a pixel size of 4.28 Å and a surface of 256 pixels 2 ) and aligning against a Gaussian sphere of matching diameter. This initial model was then scaled to that of the originally binned projections (512 pixels 2 ) and used in the subsequent reconstruction. During reconstruction, the flexible fibers of OAdV were largely masked out (460 pixel diameter ϭ 984 Å).…”

Section: Methodsmentioning

confidence: 99%

See 1 more Smart Citation

Cryoelectron Microscopy Map of Atadenovirus Reveals Cross-Genus Structural Differences from Human Adenovirus

Pantelic

Lockett

Rothnagel

et al. 2008

J Virol

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A three-dimensional (3D) cryoelectron microscopy reconstruction of the prototype Atadenovirus (OAdV [an ovine adenovirus isolate]) showing information at a 10.6-Å resolution (0.5 Fourier shell correlation) was derived by single-particle analysis. This is the first 3D structure solved for any adenovirus that is not a Mastadenovirus, allowing cross-genus comparisons between structures and the assignment of genus-specific capsid proteins. Viable OAdV mutants that lacked the genus-specific LH3 and p32k proteins in purified virions were also generated. Negatively stained 3D reconstructions of these mutants were used to identify the location of protein LH3 and infer that of p32k within the capsid. The key finding was that LH3 is a critical protein that holds the outer capsid of the virus together. In its absence, the outer viral capsid is unstable. LH3 is located in the same position among the hexon subunits as its protein IX equivalent from mastadenoviruses but sits on top of the hexon trimers, forming prominent "knobs" on the virion surface that visually distinguish OAdV from other known AdVs. Electron density was also assigned to hexon and penton subunits and to proteins IIIa and VIII. There was good correspondence between OAdV density and human AdV hexon structures, which also validated the significant differences that were observed between the penton base protein structures.The Adenoviridae comprise a large family of non-enveloped, icosahedral, generally nonpathogenic viruses with a doublestranded DNA genome (ϳ26.1 to 45 kb) (9). Because of their wide host range, viruses such as human adenovirus type 5 (AdV5) have been developed as gene delivery vectors and applied in the clinic, especially for cancer, monogenic disorders, and vaccination (http://www.wiley.co.uk/genmed /clinical/). While some of these trials have reached phases II and III, there is still considerable room for improvement in vector technology. In particular, there is strong interest in developing vectors that are targeted to specific tissues for improved therapeutic effect (6, 11), and for this purpose, structural information on the virus particle and its constituent molecules is paramount.The family Adenoviridae comprises four genera (Mastadenovirus, Aviadenovirus, Siadenovirus, and Atadenovirus). Of these, the best studied are the mastadenoviruses, which include viruses from numerous mammalian species and all known human AdVs. In contrast, members of the avi-, si-, and atadenoviruses have been isolated from birds, although the latter also occur widely in mammalian and reptilian species (9, 38). The prototype Atadenovirus, an ovine isolate (serotype 7; OAdV), is the only member for which any significant biological studies have been undertaken. OAdV uses a different (unknown) receptor from AdV5 and infects, but does not replicate in, human cells (15). It has also been developed as a gene delivery vector (2) and has regulatory approval to enter a phase I clinical trial for prostate cancer in 2008.Representative genomes from all four genera have now...

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Section: Methodsmentioning

confidence: 99%

“…OAdV uses a different (unknown) receptor from AdV5 and infects, but does not replicate in, human cells (15). It has also been developed as a gene delivery vector (2) and has regulatory approval to enter a phase I clinical trial for prostate cancer in 2008.…”

mentioning

confidence: 99%

Cryoelectron Microscopy Map of Atadenovirus Reveals Cross-Genus Structural Differences from Human Adenovirus

Pantelic

Lockett

Rothnagel

et al. 2008

J Virol

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“…OAdV.HIVA was grown on permissive CSL503 ovine fetal lung cells, and the titer was determined according to published procedures (3). In macaques, OAdV.HIVA is expected to be an attenuated nonreplicating virus as it is in all nonovine cell types that have been tested (2).…”

Section: Bcghivamentioning

confidence: 99%

“…Furthermore, we have formulated HIVA into various vaccine modalities, including plasmid DNA (21), modified vaccinia virus Ankara (MVA) (21), human adenovirus serotype 5 (HAdV-5) (5), Semliki Forest virus replicons (18,49), recombinant lysine auxotroph BCG strain Pasteur (32), and baculovirus-expressed and purified, bluetongue virus-derived chimeric NS1 tubules (37); the immunogenicity of these vectors has been compared directly and in heterologous combinations. More recently, we reported on the immunogenicity of a novel and promising vaccine vector derived from ovine atadenovirus type 7 (OAdV) (5); OAdV is the prototype member of the genus Atadenovirus, which is structurally and biologically distinct from Mastadenovirus (e.g., HAdV-5) (2,50). Importantly, no immunity to OAdV has so far been detected in human sera (26).…”

mentioning

confidence: 99%

Novel RecombinantMycobacterium bovisBCG, Ovine Atadenovirus, and Modified Vaccinia Virus Ankara Vaccines Combine To Induce Robust Human Immunodeficiency Virus-Specific CD4 and CD8 T-Cell Responses in Rhesus Macaques

Rosario

Hopkins

Fulkerson

et al. 2010

J Virol

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Mycobacterium bovis bacillus Calmette-Guérin (BCG), which elicits a degree of protective immunity against tuberculosis, is the most widely used vaccine in the world. Due to its persistence and immunogenicity, BCG has been proposed as a vector for vaccines against other infections, including HIV-1. BCG has a very good safety record, although it can cause disseminated disease in immunocompromised individuals. Here, we constructed a recombinant BCG vector expressing HIV-1 clade A-derived immunogen HIVA using the recently described safer and more immunogenic BCG strain AERAS-401 as the parental mycobacterium. Using routine ex vivo T-cell assays, BCG.HIVA 401 as a stand-alone vaccine induced undetectable and weak CD8 T-cell responses in BALB/c mice and rhesus macaques, respectively. However, when BCG.HIVA 401 was used as a priming component in heterologous vaccination regimens together with recombinant modified vaccinia virus Ankaravectored MVA.HIVA and ovine atadenovirus-vectored OAdV.HIVA vaccines, robust HIV-1-specific T-cell responses were elicited. These high-frequency T-cell responses were broadly directed and capable of proliferation in response to recall antigen. Furthermore, multiple antigen-specific T-cell clonotypes were efficiently recruited into the memory pool. These desirable features are thought to be associated with good control of HIV-1 infection. In addition, strong and persistent T-cell responses specific for the BCG-derived purified protein derivative (PPD) antigen were induced. This work is the first demonstration of immunogenicity for two novel vaccine vectors and the corresponding candidate HIV-1 vaccines BCG.HIVA 401 and OAdV.HIVA in nonhuman primates. These results strongly support their further exploration.

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“…Additionally, most of the population has been exposed to natural adenovirus infection, therefore recombinant adenovirus vectors are likely to encounter neutralizing anti-adenovirus antibodies in patient plasma. 4,5 To avoid pre-existing humoral immunity in patients, several groups have investigated adenovirus serotypes from alternative species such as cows, [6][7][8][9][10][11][12][13][14] sheep, [15][16][17][18][19][20][21][22][23][24][25] chimpanzees, [26][27][28] dogs [29][30][31][32][33][34][35][36] and chickens. [37][38][39][40] Chicken embryo lethal orphan virus (CELO; fowl adenovirus type 1), characterized as an infectious agent in 1957, 41 is attractive as a gene delivery vector since it is simple and cheap to produce in bulk in chicken embryos and has a good safety profile being completely replication defective in human cells, even in the presence of wild-type human adenovirus.…”

Section: Introductionmentioning

confidence: 99%

Chick embryo lethal orphan virus can be polymer-coated and retargeted to infect mammalian cells

et al. 2005

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Ovine atadenovirus: a review of its biology, biosafety profile and application as a gene delivery vector

Cited by 27 publications

References 52 publications

Cryoelectron Microscopy Map of Atadenovirus Reveals Cross-Genus Structural Differences from Human Adenovirus

Cryoelectron Microscopy Map of Atadenovirus Reveals Cross-Genus Structural Differences from Human Adenovirus

Novel RecombinantMycobacterium bovisBCG, Ovine Atadenovirus, and Modified Vaccinia Virus Ankara Vaccines Combine To Induce Robust Human Immunodeficiency Virus-Specific CD4 and CD8 T-Cell Responses in Rhesus Macaques

Chick embryo lethal orphan virus can be polymer-coated and retargeted to infect mammalian cells

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