Replication-defective adenovirus vectors

Tripathy SK, Black HB, Goldwasser E, Leiden JM (1996) Immune responses to transgene-encoded proteins limit the stability of gene expression after injection of replication-defective adenovirus vectors. Nat Med 2 545-550. 

A recent case concerning an fflV vaccine, which used a replication defective adenovirus type 5 (Ad5) vector, was stopped after a clinical trial showed an increase in HIV infections postvaccination. A followup investigation by Perreau et al.,96 using ex vivo modeling with dendritic cells, showed how the formation of Ad5 immune complexes, a consequence of previous adenovirus exposure, can lead to specific CD4 and 8 T cell responses, which are targeted more toward the adenovirus than the HIV antigen, and as a consequence are less protective. 

Lysosomotropic agents, such as chloroquine and sucrose, have been used to enhance DNA/vector release into the cytoplasm in vitro [187]. Viral DNA vectors have evolved the ability to escape acidified endosomes. To mimic this property, replication-defective adenoviruses were administered with transferrin-polylysine DNA vectors, resulting in greater gene expression [188,189]. More recently, endosomolytic structures have been attached to DNA vectors in lieu of using whole viruses. HA-2, the fusogenic peptide of the influenza virus... 

A major advance in replication-defective adenoviruses is the development of methods for creating recombinant viruses from distinct molecular clones in which the entire genome of the vector has been subcloned into a prokaryotic or invertebrate host. This has now been accomplished in a number of systems including yeast artificial chromosomes (21), cosmids (22), and bacterial plasmids (23-25). The subsequent discussion will focus on methods in which the adenoviral genome is subeloned in its entirety into bacterial plasmids,... 

Juillard V, Villefioy P, Godfiin D, Pavitani A, Venet A, Guillet JG. Long-term humoral and cellular immunity induced by a single immunization with replication-defective adenovirus recombinant vector. EurJ Immunol 1995 25 3467-3473. 

Reynolds and coworkers tested a differerrt strategy for selective lung delivery of adenovirus. They modified a replication-defective adertoviral vector by... 

Farina SF, Gao GP, Xiang ZQ, Rux JJ, Burnett RM, Alvira MR, Marsh J, Ertl HC, Wilson JM. Replication-defective vector based on a chimpanzee adenovirus. J Virol 2001 75 11603-13. 

Amalfitano, A., Begy, C., Chamberlain, J. S. (1996) Improved adenovirus packaging cell lines to support the growth of replication-defective gene-delivery vectors. Proc. Natl. Acad. Sci. USA 93 3352. 

The ability of two soluble chitosan formulations (chitosan and glycol chitosan) to improve the immunogenicity of an intranasaUy administered replication-defective human adenovirus type 5 expressing BoHV-1 glycoprotein D-based vaccine was investigated in cattle (Vila et al. 2004). It was reported that soluble formulation of glycol chitosan has promising potential use as an intranasal adjuvant for recombinant viral vector vaccines in cattle. 

Adeno-associated viruses are naturally defective viruses that require a helper adenovirus to replicate normally. However, they are capable of infecting a range of cells and can integrate at specific sites in human chromatin. Adeno-associated viruses have been used experimentally to kill certain forms of breast, cervical, and prostate cancer cells. As viral vectors, they have been used to introduce a gene for production of insulin and the genes for both Factor VIII and Factor IX, lacking in humans with certain forms of hemophilia (hemophilia A and B, respectively). 

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