Pathogenicity and immunogenicity of recombinant Tiantan Vaccinia Virus with deleted C12L and A53R genes

• Published in: Vaccine 2008-09, Vol.26 (39), p.5062-5071
• Main Authors: Dai, Kaifan, Liu, Ying, Liu, Mingjie, Xu, Jianqing, Huang, Wei, Huang, Xianggang, Liu, Lianxing, Wan, Yanmin, Hao, Yanling, Shao, Yiming
• Format: Article
• Language: English
• Subjects: AIDS Vaccines - genetics; AIDS Vaccines - immunology; Allergy and Immunology; Animals; Applied microbiology; Biological and medical sciences; Cytokine viroceptor genes; Enzyme-Linked Immunosorbent Assay; Female; Fundamental and applied biological sciences. Psychology; Gene Deletion; Genes; Genes, Viral; Genetic Vectors; HIV Antibodies - immunology; HIV Infections - immunology; HIV vaccine; HIV-1 - immunology; Human immunodeficiency virus; Humans; Immune system; Immunity, Cellular; Immunogenicity; Immunotherapy; Infectious diseases; Interferon-gamma - immunology; Mice; Mice, Inbred BALB C; Microbiology; Miscellaneous; Pathogenicity and immunogenicity; Pathogens; Poxvirus; Public health; Rabbits; Replicating Tiantan vaccinia virus; Smallpox; Vaccines; Vaccines, antisera, therapeutical immunoglobulins and monoclonal antibodies (general aspects); Vaccines, Attenuated - genetics; Vaccines, Attenuated - immunology; Vaccinia virus; Vaccinia virus - genetics; Vaccinia virus - immunology; Vaccinia virus - pathogenicity; Viral Proteins - genetics; Viral Proteins - immunology; Virology; Virulence
• ISSN: 0264-410X; 1873-2518
• DOI: 10.1016/j.vaccine.2008.06.011

Abstract Interest is increasing regarding replicating poxvirus as HIV vaccine vector. In China, the Tiantan Vaccinia Virus (TV) has been used most extensively in the battle of eradicating smallpox. Recently, TV was developing as vaccine vector to fight against infectious diseases such as human immunodeficiency virus (HIV). However, replicating vaccinia virus sometimes may pose serious post-vaccination complications, especially in immunosuppressed individuals. To develop a safer and more effective TV-based vector, we constructed C12L (vIL-18 binding protein) and A53R (vTNF receptor homolog) gene-deleted mutants which are based on parental TV and VTKgpe (TV expressing HIV gagpol and env gene), respectively. The pathogenicity and immunogenicity were also evaluated. Deleting these two immunomodulatory genes lessened the virulence of the parental virus in both mice and rabbit models. Notably, C12L deletion mutant attenuated the skin virulence of parental virus by as high as approximate 2 logs. Furthermore, VTKgpe with A53R and C12L gene deletion retains the high immunogenicity of the parental virus to elicit strong humoral and cellular responses to the HIV target genes despite the remarkable attenuation. These data suggest that deletion of the cytokine viroceptor gene is feasible to obtain a safer and replication-competent TV vector for vaccination and immunotherapy.