Comparative studies of several vaccinia virus strains by intrathalamic inoculation into cynomolgus monkeys

Morita, Michio; Aoyama, Yuzo; Arita, Masataka; Amano, Hiroko; Yamada, Hiroshi; Hashizume, So; Komatsu, Toshihiko; Tagaya, Isamu

doi:10.1007/bf01314664

Cited by 34 publications

(24 citation statements)

References 9 publications

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“…In an effort to develop additional safe booster antigens, we generated a recombinant vaccine based on the vaccinia virus strain DIs, which has proven not to replicate in all mammalian cells tested (25). The virologic and immunologic properties of the DIs vector have been reported previously by our group (25,26,38,70,71). The vaccinia virus DIs vector expressing SIV Gag protein elicited immune responses able to suppress SHIV infection in macaques (26).…”

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confidence: 99%

A Consecutive Priming-Boosting Vaccination of Mice with Simian Immunodeficiency Virus (SIV)gag/polDNA and Recombinant Vaccinia Virus Strain DIs Elicits Effective Anti-SIV Immunity

Someya

Xin

Matsuo

et al. 2004

J Virol

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To evaluate immunity induced by a novel DNA prime-boost regimen, we constructed a DNA plasmid encoding the gag and pol genes from simian immunodeficiency virus (SIV) (SIVgag/pol DNA), in addition to a replication-deficient vaccinia virus strain DIs recombinant expressing SIV gag and pol genes (rDIsSIVgag/pol). In mice, priming with SIVgag/pol DNA, followed by rDIsSIVgag/pol induced an SIV-specific lymphoproliferative response that was mediated by a CD4؉ -T-lymphocyte subset. Immunization with either vaccine alone was insufficient to induce high levels of proliferation or Th1 responses in the animals. The prime-boost regimen also induced SIV Gag-specific cellular responses based on gamma interferon secretion, as well as cytotoxic-T-lymphocyte responses. Thus, the regimen of DNA priming and recombinant DIs boosting induced Th1-type cell-mediated immunity, which was associated with resistance to viral challenge with wild-type vaccinia virus expressing SIVgag/pol, suggesting that this new regimen may hold promise as a safe and effective vaccine against human immunodeficiency virus type 1.

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confidence: 99%

A Consecutive Priming-Boosting Vaccination of Mice with Simian Immunodeficiency Virus (SIV)gag/polDNA and Recombinant Vaccinia Virus Strain DIs Elicits Effective Anti-SIV Immunity

Someya

Xin

Matsuo

et al. 2004

J Virol

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“…m8, a variant that forms small-sized pocks, is a direct descendant of mO, which itself is a clone that forms medium-sized pocks, isolated from the LC16 strain (5). LC16 was selected from LO based on its temperature sensitivity (5,7,8). In rabbit and monkey models, the neurovirulence of m8 was markedly reduced in comparison with other vaccine strains (5,(7)(8)(9), including LO and Dryvax (10,11), and comparable to the replication-defective mutant DIs (Dairen I-derived smallsized pock variant) (12).…”

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confidence: 99%

“…LC16 was selected from LO based on its temperature sensitivity (5,7,8). In rabbit and monkey models, the neurovirulence of m8 was markedly reduced in comparison with other vaccine strains (5,(7)(8)(9), including LO and Dryvax (10,11), and comparable to the replication-defective mutant DIs (Dairen I-derived smallsized pock variant) (12). Moreover, m8 exhibited a markedly diminished dermal reaction in both rabbits and humans and a lower fever ratio compared with mO in clinical trials (5,6).…”

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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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“…However, a single nucleotide insertion just upstream of the m8 B5R mutation site has recently been reported to restore the ORF to the parental mO phenotype after repeated (10 or more) virus passages. Although the repaired viruses were a marginal population, attenuation that is achieved by a deletion of the whole B5R gene prevented the reversion of m8-to mO-type viruses (32), which have, however, much lower virulence than LO and NYBH (24,25,39). In turn, the genetic manipulation of m8 to replace genes related to protective immunity, but not to pathogenicity, with the counterpart genes of VAR may make m8 more efficacious.…”

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confidence: 99%

“…The m8 virus exhibited the lowest levels of neurovirulence and the mildest adverse events among several vaccine strains, such as NYBH, CV1, and EM63, in monkeys, rabbits, and cortisone-induced immunocompromised mice (24,38,39). Its antigenicity was as high as that of the LO vaccine, not only in animals, but also in approximately 50,000 Japanese children vaccinated from 1973 to 1974 (over 90,000 doses in 1974 and 1975) with no reports of severe complications (24,57).…”

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An Attenuated LC16m8 Smallpox Vaccine: Analysis of Full-Genome Sequence and Induction of Immune Protection

Morikawa¹,

Sakiyama

Hasegawa

et al. 2005

J Virol

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The potential threat of smallpox bioterrorism has made urgent the development of lower-virulence vaccinia virus vaccines. An attenuated LC16m8 (m8) vaccine was developed in 1975 from the Lister strain used in the World Health Organization smallpox eradication program but was not used against endemic smallpox. Today, no vaccines can be tested with variola virus for efficacy in humans, and the mechanisms of immune protection against the major intracellular mature virion (IMV) and minor extracellular enveloped virion (EEV) populations of poxviruses are poorly understood. Here, we determined the full-genome sequences of the m8, parental LC16mO (mO), and grandparental Lister (LO) strains and analyzed their evolutionary relationships. Sequence data and PCR analysis indicated that m8 was a progeny of LO and that m8 preserved almost all of the open reading frames of vaccinia virus except for the disrupted EEV envelope gene B5R. In accordance with this genomic background, m8 induced 100% protection against a highly pathogenic vaccinia WR virus in mice by a single vaccination, despite the lack of anti-B5R and anti-EEV antibodies. The immunogenicity and priming efficacy with the m8 vaccine consisting mainly of IMV were as high as those with the intact-EEV parental mO and grandparental LO vaccines. Thus, mice vaccinated with 10 7 PFU of m8 produced low levels of anti-B5R antibodies after WR challenge, probably because of quick clearance of B5R-expressing WR EEV by strong immunity induced by the vaccination. These results suggest that priming with m8 IMV provides efficient protection despite undetectable levels of immunity against EEV.

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Comparative studies of several vaccinia virus strains by intrathalamic inoculation into cynomolgus monkeys

Cited by 34 publications

References 9 publications

A Consecutive Priming-Boosting Vaccination of Mice with Simian Immunodeficiency Virus (SIV)gag/polDNA and Recombinant Vaccinia Virus Strain DIs Elicits Effective Anti-SIV Immunity

A Consecutive Priming-Boosting Vaccination of Mice with Simian Immunodeficiency Virus (SIV)gag/polDNA and Recombinant Vaccinia Virus Strain DIs Elicits Effective Anti-SIV Immunity

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

An Attenuated LC16m8 Smallpox Vaccine: Analysis of Full-Genome Sequence and Induction of Immune Protection

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