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Host range restricted, non-replicating vaccinia virus vectors as vaccine candidates

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TLDR
The potential usefulness of recombinant MVA for prophylactic vaccination and therapeutic treatment of infectious diseases and cancer is suggested and previous data on the safety of MVA in humans is suggested.
Abstract
The use of a recombinant virus containing a heterologous gene of another microorganism as a live vaccine was suggested more than 10 years ago (Mackett et al, 1982; Panicali and Paoletti, 1982). Vaccinia virus was considered for such a purpose because of its success as a smallpox vaccine and ease and economy of production, distribution and administration (Fermer et al., 1988). The extensive experimental use of recombinant vaccinia viruses was facilitated by the construction of plasmid transfer vectors containing a vaccinia virus promoter, one or more convenient restriction endonuclease sites for inserting a foreign gene, flanking DNA sequences for homologous recombination into a non-essential site of the vaccinia virus genome and for selection and/or screening of recombinant viruses (Chakrabarti et al., 1985; Mackett et al., 1984). Humoral and cell mediated immune responses to an expressed foreign protein and protection of experimental animals against challenge with the corresponding pathogen were demonstated in a variety of animal model systems (Cox et al., 1992; Moss, 1991).

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Journal ArticleDOI

Modified vaccinia virus Ankara undergoes limited replication in human cells and lacks several immunomodulatory proteins: implications for use as a human vaccine.

TL;DR: It is demonstrated that MVA can replicate, albeit poorly, in transformed human cell lines, but not in primary human fibroblasts although there is limited cell-to-cell spread and MVA is a potent inducer of type I interferon (IFN) from primary human cells, which may restrict virus spread in vivo.
Journal ArticleDOI

Smallpox vaccine–induced antibodies are necessary and sufficient for protection against monkeypox virus

TL;DR: It is reported that vaccinia-specific B-cell responses are essential for protection of macaques from monkeypox virus, a variola virus ortholog, and vaccines able to induce long-lasting protective antibody responses may constitute realistic alternatives to the currently available smallpox vaccine.
Journal ArticleDOI

Highly attenuated modified vaccinia virus Ankara replicates in baby hamster kidney cells, a potential host for virus propagation, but not in various human transformed and primary cells.

TL;DR: Baby hamster kidney cells (BHK), a well-characterized, easily maintained cell line, supported MVA growth and as proficient expression of the E. coli lacZ reporter gene as the highly efficient CEF, whereas other cell lines were non-permissive or allowed only very limited MVA replication.
Journal ArticleDOI

Biology of Attenuated Modified Vaccinia Virus Ankara Recombinant Vector in Mice: Virus Fate and Activation of B- and T-Cell Immune Responses in Comparison with the Western Reserve Strain and Advantages as a Vaccine

TL;DR: It is found that MVA infects the same target tissues as the WR strain; surprisingly, within 6 h postinoculation the levels of expression of antigens were higher in tissue from MVA-infected mice than in tissues from mice infected with wild-type virus but at later times postinOCulation were 2 to 4 log units higher in tissuesfrom WR-infecting mice.
References
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Book

Smallpox and its eradication

Frank Fenner
TL;DR: The author worked for the smallpox eradi-cation programme in western Africa in 1962-1963 as a member of the staff of the W H O Regional Office for Africa, and joined the Smallpox Eradication unit, of which he was Chief from 1977 until 1984.
Journal ArticleDOI

Protective effects of a live attenuated SIV vaccine with a deletion in the nef gene.

TL;DR: Rhesus monkeys vaccinated with live SIV deleted in nef were completely protected against challenge by intravenous inoculation of live, pathogenic SIV.
Journal ArticleDOI

Vaccinia virus expression vector: coexpression of beta-galactosidase provides visual screening of recombinant virus plaques.

TL;DR: Each protocol was tested by constructing vaccinia virus recombinants that express hepatitis B virus surface antigen by constructing plasmid coexpression vector that directs the insertion of a foreign gene of interest together with the Escherichia coli beta-galactosidase (beta gal) gene into the thymidine kinase (TK) locus of the vaccinations genome.
Journal ArticleDOI

Vaccinia virus: a selectable eukaryotic cloning and expression vector

TL;DR: These studies demonstrate the use ofvaccinia virus as a selectable cloning and expression vector, confirm the map location of the vaccinia virus TK gene, and provide initial information regarding the location of vacciniairus transcriptional regulatory sequences.
Journal ArticleDOI

General method for production and selection of infectious vaccinia virus recombinants expressing foreign genes.

TL;DR: The production and selection of infectious vaccinia virus recombinants expressing foreign genes was facilitated by the construction of plasmid vectors and Infectious recombinant viruses expressing the procaryotic enzyme chloramphenicol acetyltransferase were constructed to optimize the system.
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