MVA-Stufenimpfung gegen Pocken

Stickl, H; Hochstein‐Mintzel, V.; Mayr, Anton; Huber, H C; Schäfer, H; Holzner, A

doi:10.1055/s-0028-1108143

Cited by 197 publications

(71 citation statements)

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“…m8rc (plaque-purified m8 to minimize contamination by revertants) and the revertant viruses (LPCs) were isolated from the m8 stock by three serial plaque purifications in RK13 cells. The modified VV Ankara (MVA) (26,27) and Western Reserve (WR) viruses were obtained from S. Morikawa (National Institute of Infectious Diseases, Tokyo). MVA was propagated and titrated in chicken embryo fibroblasts.…”

Section: Methodsmentioning

confidence: 99%

Genetically stable and fully effective smallpox vaccine strain constructed from highly attenuated vaccinia LC16m8

Kidokoro

Tashiro

Shida

2005

Proc. Natl. Acad. Sci. U.S.A.

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A highly attenuated LC16m8 (m8) smallpox vaccine has been licensed in Japan because of its extremely low neurovirulence profile, which is comparable to that of replication incompetent strains of vaccinia virus. From 1973 to 1975, m8 was administrated to >100,000 infants where it induced levels of immunity similar to that of the originating Lister strain, without any serious side effects. Recently, we observed that m8 reverts spontaneously to large plaque forming clones that possess virulence equivalent to that of LC16mO, a parental virus strain of m8. Here, we report that the B5R gene is responsible for the reversion, and that we could construct a more genetically stable virus by deleting B5R from m8. The protective immunogenicity of the vaccine candidate proved to be equivalent to that of the U.S.-licensed product Dryvax, and much superior to modified vaccinia Ankara in a mouse model. Furthermore, the vaccine strain never elicited any symptoms in severe combined immunodeficiency disease mice, even at a dose 1,000-fold greater than that used in the immune protection experiments, which is in contrast to the lethal pathogenicity induced by Dryvax inoculation of severe combined immunodeficiency disease mice. Our results suggest that this vaccine strain is a good candidate as a suitable smallpox vaccine and a vector virus, and that B5R is not essential for protective immunity against smallpox.B5R gene ͉ reversion ͉ Lister strain ͉ extracellular enveloped virion

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Section: Methodsmentioning

confidence: 99%

Genetically stable and fully effective smallpox vaccine strain constructed from highly attenuated vaccinia LC16m8

Kidokoro

Tashiro

Shida

2005

Proc. Natl. Acad. Sci. U.S.A.

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“…The host range of this strain is severely restricted as it replicates only in CEFs. MVA has been proven to be avirulent in a variety of animals even under immunosuppression (for review see Mayr et al, 1978;Stickl et al, 1974). It has been used without complications in primary vaccinations in over 120000 humans (Mayr & Danner, 1979).…”

Section: Introductionmentioning

confidence: 99%

Mapping of deletions in the genome of the highly attenuated vaccinia virus MVA and their influence on virulence

Meyer

Sutter²,

Mayr³

1991

Journal of General Virology

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427

351

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Different passages of the vaccinia virus strain Ankara (CVA wild-type) during attenuation to MVA (modified vaccinia virus Ankara) have been analysed to detect alterations in the genome. Physical maps for the restriction enzymes HindlII and XhoI have been established. Six major deletions relative to the wildtype strain CVA could be localized. They reduce the size of the entire genome from 208 kb (CVA wild-type) to 177 kb for the MVA strain. Four deletions occurred during the first 382 passages and the resulting variant (CVA 382) displays an attenuated phenotype similar to that of the MVA strain. The deletions are located in both terminal fragments, affect two-thirds of the host range gene K1L and eliminate 3.5 kb of a highly conserved region in the HindlII A fragment. During the next 190 passages leading to MVA two additional deletions appeared. Again, one is located in the left terminal fragment, and the other includes the A-type inclusion body gene. Neither of the deletions appear to participate in further attenuation of the virus. Rescue of the partially deleted host range region with the corresponding wild-type DNA restored the ability of the attenuated strains MVA and CVA 382 to grow in some non-permissive tissue cultures. Nevertheless, the complete host range of the wild-type strain was not recovered. Also, plaque-forming behaviour and reduced virulence were not influenced. From the data presented it may be concluded that the partially deleted host range gene is not solely responsible for attenuation.

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“…Compared to VV, strain Copenhagen, about onethird of the MVA genes are deleted or inactive, genes that encode in particular for host range and immune evasion factors and are located on the left-and right-hand sides of the genome (1). When tested as a putative vaccine against smallpox, the MVA caused none of the side effects observed with replication-competent strains while eliciting an immunoresponse (12,24). More recently, MVA has become an important candidate for use as a live vaccine against other pathogens and in the treatment of certain forms of cancer (reviewed in reference 10).…”

mentioning

confidence: 99%

Plasma Membrane Budding as an Alternative Release Mechanism of the Extracellular Enveloped Form of Vaccinia Virus from HeLa Cells

Meiser

Sancho

Locker

2003

J Virol

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MVA-Stufenimpfung gegen Pocken

Cited by 197 publications

References 1 publication

Genetically stable and fully effective smallpox vaccine strain constructed from highly attenuated vaccinia LC16m8

Genetically stable and fully effective smallpox vaccine strain constructed from highly attenuated vaccinia LC16m8

Mapping of deletions in the genome of the highly attenuated vaccinia virus MVA and their influence on virulence

Plasma Membrane Budding as an Alternative Release Mechanism of the Extracellular Enveloped Form of Vaccinia Virus from HeLa Cells

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