title: Genetically stable and fully effective smallpox vaccine strain constructed from highly attenuated vaccinia LC16m8.
abstract: 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.
authors.affiliation: Department of Virology III, National Institute of Infectious Diseases, 4-7-1 Gakuen, Musashimurayama, Tokyo 208-0011, Japan. kidokoro@nih.go.jp
authors.forename: Minoru
authors.initials: M
authors.lastname: Kidokoro
authors.forename: Masato
authors.initials: M
authors.lastname: Tashiro
authors.forename: Hisatoshi
authors.initials: H
authors.lastname: Shida
mesh_terms: D000818:Animals; D004306:Dose-Response Relationship, Immunologic; D005260:Female; D008562:Membrane Glycoproteins / Q000276:immunology; D051379:Mice; D008807:Mice, Inbred BALB C; D016513:Mice, SCID; D011817:Rabbits; D012900:Smallpox Vaccine / Q000276:immunology*; D013997:Time Factors; D014613:Vaccines, Attenuated / Q000276:immunology; D014616:Vaccinia virus / Q000276:immunology*; D014759:Viral Envelope Proteins / Q000276:immunology
chemical_list: D008562:Membrane Glycoproteins; D012900:Smallpox Vaccine; D014613:Vaccines, Attenuated; D014759:Viral Envelope Proteins; C074512:42kDa protein, Vaccinia virus