Particle heterogeneity in vaccinia virus populations during passage

Gangemi, J. David; Sharp, D. G.

doi:10.1016/0042-6822(78)90430-0

Cited by 4 publications

(2 citation statements)

References 19 publications

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“…It has long been recognized that vaccinia virus represents a heterogeneous swarm of virus subpopulations that differ biologically and molecularly. 11 This variation became especially important as vaccinia was developed as a live vector for foreign genes. Plaque-purified vaccinia virus lines were shown to differ significantly in neurovirulence for mice, in their ability to evoke immune responses against the inserted gene product, and in their HindIII restriction maps.…”

Section: Discussionmentioning

confidence: 99%

ACAM2000 clonal Vero cell culture vaccinia virus (New York City Board of Health strain) – a second-generation smallpox vaccine for biological defense

Monath

CALDWELL

Mundt

et al. 2004

International Journal of Infectious Diseases

120

118

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The threat of smallpox as a biological weapon has spurred efforts to create stockpiles of vaccine for emergency preparedness. In lieu of preparing vaccine in animal skin (the original method), we cloned vaccinia virus (New York City Board of Health strain, Dryvax by plaque purification and amplified the clone in cell culture. The overarching goal was to produce a modern vaccine that was equivalent to the currently licensed Dryvax in its preclinical and clinical properties, and could thus reliably protect humans against smallpox. A variety of clones were evaluated, and many were unacceptably virulent in animal models. One clonal virus (ACAM1000) was selected and produced at clinical grade in MRC-5 human diploid cells. ACAM1000 was comparable to Dryvax in immunogenicity and protective activity but was less neurovirulent for mice and nonhuman primates. To meet requirements for large quantities of vaccine after the events of September 11th 2001, the ACAM1000 master virus seed was used to prepare vaccine (designated ACAM2000) at large scale in Vero cells under serum-free conditions. The genomes of ACAM1000 and ACAM2000 had identical nucleotide sequences, and the vaccines had comparable biological phenotypes. ACAM1000 and ACAM2000 were evaluated in three Phase 1 clinical trials. The vaccines produced major cutaneous reactions and evoked neutralizing antibody and cell-mediated immune responses in the vast majority of subjects and had a reactogenicity profile similar to that of Dryvax.

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Section: Discussionmentioning

confidence: 99%

ACAM2000 clonal Vero cell culture vaccinia virus (New York City Board of Health strain) – a second-generation smallpox vaccine for biological defense

Monath

CALDWELL

Mundt

et al. 2004

International Journal of Infectious Diseases

120

118

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“…The host range mutants were interpreted to be defective in some control function required for virus replication (8). Subsequent genomic analysis of these rabbitpox virus mutants (18,25) demonstrated extensive terminal deletions (up to 30 kilobases [kb]) of DNA. Host range mutants of vaccinia virus have also been described (4, 5,10,15,22,39). Nitrous acid mutagenesis of the Copenhagen strain of vaccinia virus allowed Drillien et al (4) to isolate a host range mutant defective in replication in most human cells.…”

mentioning

confidence: 99%

Cloning and expression of foreign genes in vaccinia virus, using a host range selection system

Perkus

Limbach

Paoletti

1989

J Virol

146

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A simple selection system has been developed for the cloning and expression of open reading frames in vaccinia virus. The selection system is based on a conditional lethal (host range) mutant of vaccinia virus. A deletion mutant of the vaccinia virus WR strain was generated by insertion of the neomycin resistance gene from transposon Tn5 and selection with the antibiotic G418. This deletion recombinant, vP293, lacked approximately 21.7 kilobases of DNA beginning 3.8 kilobases from the left end of the genome. vP293 was capable of plaquing on primary chicken embryo fibroblasts and two monkey cell lines (BSC-40 and Vero) but was defective in replication in the human cell line MRC-5. Insertion of the host range gene KIL into vP293 restored the ability to grow on MRC-5 cells. A series of plasmids were constructed which in addition to the KIL gene contained a vaccinia virus early-late promoter, H6, followed by a unique polylinker sequence, translational initiation and termination signals, and an early transcription termination signal. These plasmids, pHESI through 4, allowed for rapid single-step cloning and expression of any open reading frame when recombined in vivo with vP293 and scored for growth on MRC-5 cells.

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