A Novel System for Constructing a Recombinant Highly-Attenuated Vaccinia Virus Strain (LC16m8) Expressing Foreign Genes and Its Application for the Generation of LC16m8-Based Vaccines against Herpes Simplex Virus 2

• Published in: Japanese Journal of Infectious Diseases Vol. 71; no. 3; pp. 229 - 233
• Main Authors: Omura, Natsumi, Yoshikawa, Tomoki, Fujii, Hikaru, Shibamura, Miho, Inagaki, Takuya, Kato, Hirofumi, Egawa, Kazutaka, Harada, Shizuko, Yamada, Souichi, Takeyama, Haruko, Saijo, Masayuki
• Format: Journal Article
• Language: English
• Published: Japan National Institute of Infectious Diseases, Japanese Journal of Infectious Diseases Editorial Committee 2018; Japan Science and Technology Agency
• Subjects: Dosage; Fatalities; Fluorescence; Genes; Glycoprotein B; Glycoproteins; Herpes simplex; Herpes viruses; Immunoglobulin G; LC16m8; Lethal dose; Mice; Smallpox; Survival; Vaccine; Vaccine efficacy; Vaccines; Vaccinia virus; Viruses; LC16m8; Vaccinia virus; Vaccine
• ISSN: 1344-6304; 1884-2836; 1884-2836
• DOI: 10.7883/yoken.JJID.2017.458

A novel system was developed for generating highly attenuated vaccinia virus LC16m8 (m8, third-generation smallpox vaccine) that expresses foreign genes. The innovations in this system are its excisable selection marker, specificity of the integration site of a gene of interest, and easy identification of clones with a fluorescent signal. Using this system, recombinant m8s, which expressed herpes simplex virus 2 (HSV-2) glycoprotein B (gB)-, gD-, or both gB and gD (gB + gD), were generated, and their efficacy was evaluated. First, the induction of a specific IgG against these HSV-2 glycoproteins in mice infected with one of these recombinant m8s was confirmed by an immunofluorescent assay. Next, mice preinfected with one of the recombinant m8s were infected with HSV-2 at a lethal dose to examine the vaccine efficacy. The fatality rate among the mice preinfected with either the recombinant gB + gD- or gD-expressing m8 significantly decreased in comparison with the control. The survival rate in male and female mice preinfected with either the recombinant gB + gD- or gD-expressing m8 increased to 100% and 60%, respectively, while most of the control mice died. In summary, this new system may be applicable to creation of a novel m8-based vaccine.