Vaccinia Virus LC16m8∆ as a Vaccine Vector for Clinical Applications
AbstractThe 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
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Kidokoro, M.; Shida, H. Vaccinia Virus LC16m8∆ as a Vaccine Vector for Clinical Applications. Vaccines 2014, 2, 755-771.
Kidokoro M, Shida H. Vaccinia Virus LC16m8∆ as a Vaccine Vector for Clinical Applications. Vaccines. 2014; 2(4):755-771.Chicago/Turabian Style
Kidokoro, Minoru; Shida, Hisatoshi. 2014. "Vaccinia Virus LC16m8∆ as a Vaccine Vector for Clinical Applications." Vaccines 2, no. 4: 755-771.