Immunogenicity and Safety of Defective Vaccinia Virus Lister: Comparison with Modified Vaccinia Virus Ankara

Ober, Bertram T.; Brühl, P; Schmidt, Michaela; Wieser, Verena; Gritschenberger, W.; Coulibaly, Sogue; Savidis-Dacho, Helga; Gerenčer, Marijan; Falkner, Falko G.

doi:10.1128/jvi.76.15.7713-7723.2002

Cited by 57 publications

(51 citation statements)

References 38 publications

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“…The viral attenuation by expression of IFN-␤ without cost to vaccine immunogenicity suggests that such vaccines can be used as alternatives to the currently available smallpox vaccine. Several studies have been conducted to test the ability of using rVV such as modified VV Ankara as a safer smallpox vaccine that can induce an effective immune response without replication of the VV (51,52). Similar to our characterization of HA-VV-IFN-␤, modified VV Ankara is highly attenuated and yet it induces a robust immune response upon vaccination that can protect against challenge by virulent poxviruses.…”

Section: Discussionmentioning

confidence: 64%

Differential Effects of the Type I Interferons α4, β, and ε on Antiviral Activity and Vaccine Efficacy

Day

Ramshaw

Ramsay

et al. 2008

The Journal of Immunology

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The type I IFNs exert a range of activities that include antiviral, antiproliferative, and immunomodulatory effects. To study this further, we have constructed recombinant vaccinia viruses expressing HIV or hemagglutinin (HA) Ags along with murine type I IFNs, IFN-α4 (HA-VV-IFN-α4), IFN-β (HA-VV-IFN-β), or IFN-ε (HIV-VV-IFN-ε), a recently discovered member of this family. Our aims were to characterize IFN-ε functionality as a type I IFN and also to study the biological properties of these factors toward the development of safer and more effective vector-based vaccines. HIV-VV-IFN-ε and HA-VV-IFN-β grew to lower titers than did their parental controls in murine cell lines. In vivo, however, HIV-VV-IFN-ε growth was not attenuated, while IFN-β demonstrated potent local antiviral activity with no replication of HA-VV-IFN-β detected. Flow cytofluorometric analysis of B lymphocytes incubated with virally encoded IFN-ε showed up-regulation of activation markers CD69 and CD86, while RT-PCR of IFN-ε-treated cells revealed that gene expression levels of antiviral proteins were elevated, indicating the induction of an antiviral state. The use of these constructs in a poxvirus prime-boost immunization regime led to robust humoral and cellular immune responses against the encoded Ags, despite the lack of replication in the case of HA-VV-IFN-β. Thus, coexpression of these factors may be beneficial in the design of safer vector-based vaccines. Our data also indicate that while IFN-ε exhibits certain biological traits similar to other type I IFNs, it may also have a specific role in mucosal immune regulation that is quite distinct.

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Section: Discussionmentioning

confidence: 64%

Differential Effects of the Type I Interferons α4, β, and ε on Antiviral Activity and Vaccine Efficacy

Day

Ramshaw

Ramsay

et al. 2008

The Journal of Immunology

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“…Recently, several groups have reevaluated the available vaccinia strains, including the replication-defective MVA, in a search for safer smallpox vaccines (37)(38)(39)(40). Although 10 9 pfu of MVA was shown to be safe in monkeys (41), a large quantity of virus, 10 8 pfu, an amount that is 1,000-fold more than a conventional vaccination dosage, was necessary to induce protective immunity (40).…”

Section: Discussionmentioning

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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“…3) This vaccination regimen consisted of DNA and a nonreplicating vaccinia virus DIs, which is very safe even in immunodeficient states. Although other highly attenuated vaccinia strains replicate under synchronized viral infections to mammalian cells (37,38), the DIs does not replicate in any mammalian cells tested because of natural big deletion of the genome (22, 23, 39). Thus, DIs vaccination eliminates the risk of a disseminated or progressive vaccinia viral infection in the immunocompromised, HIVinfected individual.…”

Section: Discussionmentioning

confidence: 99%

“…The currently widely used MVA, which was developed toward the end of the campaign to eradicate small pox, has been effectively and safely used in Ͼ100,000 people as a small pox vaccine (19). MVA-based recombinant vector has also been reported to be safe in animals (20,21). Lately, we have developed a replication-defective vaccinia virus DIs strain as a vaccine vector (22,23).…”

Section: Induction Of Positive Cellular and Humoral Immune Responses mentioning

confidence: 99%

Induction of Positive Cellular and Humoral Immune Responses by a Prime-Boost Vaccine Encoded with Simian Immunodeficiency Virusgag/pol

Someya

Ami

Nakasone

et al. 2006

The Journal of Immunology

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It is believed likely that immune responses are responsible for controlling viral load and infection. In this study, when macaques were primed with plasmid DNA encoding SIV gag and pol genes (SIVgag/pol DNA) and then boosted with replication-deficient vaccinia virus DIs recombinant expressing the same genes (rDIsSIVgag/pol), this prime-boost regimen generated higher levels of Gag-specific CD4+ and CD8+ T cell responses than did either SIVgag/pol DNA or rDIsSIVgag/pol alone. When the macaques were i.v. challenged with pathogenic simian/HIV, the prime-boost group maintained high CD4+ T cell counts and reduced plasma viral loads up to 30 wk after viral challenge, whereas the rDIsSIVgag/pol group showed only a partial attenuation of the viral infection, and the group immunized with SIVgag/pol DNA alone showed none at all. The protection levels were better correlated with the levels of virus-specific T cell responses than the levels of neutralization Ab responses. These results demonstrate that a vaccine regimen that primes with DNA and then boosts with a replication-defective vaccinia virus DIs generates anti-SIV immunity, suggesting that it will be a promising vaccine regimen for HIV-1 vaccine development.

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Immunogenicity and Safety of Defective Vaccinia Virus Lister: Comparison with Modified Vaccinia Virus Ankara

Cited by 57 publications

References 38 publications

Differential Effects of the Type I Interferons α4, β, and ε on Antiviral Activity and Vaccine Efficacy

Differential Effects of the Type I Interferons α4, β, and ε on Antiviral Activity and Vaccine Efficacy

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

Induction of Positive Cellular and Humoral Immune Responses by a Prime-Boost Vaccine Encoded with Simian Immunodeficiency Virusgag/pol

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