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Vaccinia Virus LC16m8∆ as a Vaccine Vector for Clinical Applications.

Kidokoro M, Shida H - Vaccines (Basel) (2014)

Bottom Line: 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.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 Article: PubMed Central - PubMed

Affiliation: Department of Virology III, National Institute of Infectious Diseases, 4-7-1 Gakuen, Musashimurayama-shi, Tokyo 208-0011, Japan. kidokoro@nih.go.jp.

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.

No MeSH data available.


Related in: MedlinePlus

Genetic stability of LC16m8∆ and LC16m8 upon serial passage in primary rabbit kidney cells at different temperatures (30 °C or 34 °C). Figure modified from Kidokoro et al. [34]. LPC, large-plaque-forming clone.
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vaccines-02-00755-f002: Genetic stability of LC16m8∆ and LC16m8 upon serial passage in primary rabbit kidney cells at different temperatures (30 °C or 34 °C). Figure modified from Kidokoro et al. [34]. LPC, large-plaque-forming clone.

Mentions: The genetic stability of LC16m8∆ was evaluated by serial passage in primary rabbit kidney (PRK) cells, which were used to generate the LC16m8 vaccine. No detectable LPCs emerged from LC16m8∆ under any of the test conditions, including those used in vaccine production (passage in PRK cells at 30 °C). By contrast, LPCs emerged from LC16m8 that was plaque-purified immediately before testing (Figure 2). It should be noted that once LPCs appeared in the cultures, the LPCs:LC16m8 ratio increased rapidly with the passage number (Figure 2).


Vaccinia Virus LC16m8∆ as a Vaccine Vector for Clinical Applications.

Kidokoro M, Shida H - Vaccines (Basel) (2014)

Genetic stability of LC16m8∆ and LC16m8 upon serial passage in primary rabbit kidney cells at different temperatures (30 °C or 34 °C). Figure modified from Kidokoro et al. [34]. LPC, large-plaque-forming clone.
© Copyright Policy
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4494248&req=5

vaccines-02-00755-f002: Genetic stability of LC16m8∆ and LC16m8 upon serial passage in primary rabbit kidney cells at different temperatures (30 °C or 34 °C). Figure modified from Kidokoro et al. [34]. LPC, large-plaque-forming clone.
Mentions: The genetic stability of LC16m8∆ was evaluated by serial passage in primary rabbit kidney (PRK) cells, which were used to generate the LC16m8 vaccine. No detectable LPCs emerged from LC16m8∆ under any of the test conditions, including those used in vaccine production (passage in PRK cells at 30 °C). By contrast, LPCs emerged from LC16m8 that was plaque-purified immediately before testing (Figure 2). It should be noted that once LPCs appeared in the cultures, the LPCs:LC16m8 ratio increased rapidly with the passage number (Figure 2).

Bottom Line: 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.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 Article: PubMed Central - PubMed

Affiliation: Department of Virology III, National Institute of Infectious Diseases, 4-7-1 Gakuen, Musashimurayama-shi, Tokyo 208-0011, Japan. kidokoro@nih.go.jp.

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.

No MeSH data available.


Related in: MedlinePlus