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Vaccines 2014, 2(4), 755-771; doi:10.3390/vaccines2040755

Vaccinia Virus LC16m8∆ as a Vaccine Vector for Clinical Applications

1,†
and
2,†,*
1
Department of Virology III, National Institute of Infectious Diseases, 4-7-1 Gakuen, Musashimurayama-shi, Tokyo 208-0011, Japan
2
Institute for Genetic Medicine, Hokkaido University, Kita-15, Nishi-7, Kita-ku, Sapporo 060-0815, Japan
These authors contributed equally to this work.
*
Author to whom correspondence should be addressed.
Received: 3 June 2014 / Revised: 16 September 2014 / Accepted: 28 September 2014 / Published: 17 October 2014
(This article belongs to the Special Issue Vaccine Vector)
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Abstract

The LC16m8 strain of vaccinia virus, the active ingredient in the Japanese smallpox vaccine, was derived from the Lister/Elstree strain. LC16m8 is replication-competent and has been administered to over 100,000 infants and 3,000 adults with no serious adverse reactions. Despite this outstanding safety profile, the occurrence of spontaneously-generated large plaque-forming virulent LC16m8 revertants following passage in cell culture is a major drawback. We identified the gene responsible for the reversion and deleted the gene (B5R) from LC16m8 to derive LC16m8Δ. LC16m8∆ is non-pathogenic in immunodeficient severe combined immunodeficiency (SCID) mice, genetically-stable and does not reverse to a large-plaque phenotype upon passage in cell culture, even under conditions in which most LC16m8 populations are replaced by revertants. Moreover, LC16m8∆ is >500-fold more effective than the non-replicating vaccinia virus (VV), Modified Vaccinia Ankara (MVA), at inducing murine immune responses against pathogenic VV. LC16m8∆, which expresses the SIV gag gene, also induced anti-Gag CD8+ T-cells more efficiently than MVA and another non-replicating VV, Dairen I minute-pock variants (DIs). Moreover, LC16m8∆ expressing HIV-1 Env in combination with a Sendai virus vector induced the production of anti-Env antibodies and CD8+ T-cells. Thus, the safety and efficacy of LC16m8∆ mean that it represents an outstanding platform for the development of human vaccine vectors. View Full-Text
Keywords: LC16m8∆; LC16m8; vaccinia virus; reversion; B5R; MVA; DIs; SIV; HIV LC16m8∆; LC16m8; vaccinia virus; reversion; B5R; MVA; DIs; SIV; HIV
This is an open access article distributed under the Creative Commons Attribution License which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. (CC BY 4.0).

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MDPI and ACS Style

Kidokoro, M.; Shida, H. Vaccinia Virus LC16m8∆ as a Vaccine Vector for Clinical Applications. Vaccines 2014, 2, 755-771.

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