Vaccinia Virus LC16m8∆ as a Vaccine Vector for Clinical Applications

Vaccines

Minoru Kidokoro¹ 

[1] Department of Virology III, National Institute of Infectious Diseases, 4-7-1 Gakuen, Musashimurayama-shi, Tokyo 208-0011, Japan; E-Mail:

关键词: LC16m8∆;    LC16m8;    vaccinia virus;    reversion;    B5R;    MVA;    DIs;    SIV;    HIV;   

DOI  :  10.3390/vaccines2040755

来源: mdpi

【 摘 要 】

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.

【 授权许可】

CC BY   
© 2014 by the authors; licensee MDPI, Basel, Switzerland.