Vaccinia viruses with mutations in the E3L gene as potential replication-competent, attenuated vaccines: Scarification vaccination

• Published in: Vaccine 2008-06, Vol.26 (23), p.2860-2872
• Main Authors: Jentarra, Garilyn M, Heck, Michael C, Youn, Jin Won, Kibler, Karen, Langland, Jeffrey O, Baskin, Carole R, Ananieva, Olga, Chang, Yung, Jacobs, Bertram L
• Format: Article
• Language: English
• Subjects: Administration, Intranasal; Allergy and Immunology; Animals; Antibodies, Viral - analysis; Antibodies, Viral - biosynthesis; Antiviral Agents - pharmacology; Applied microbiology; Biological and medical sciences; Cells, Cultured; Comet Assay; Cricetinae; Cytokines - biosynthesis; Drug Resistance, Viral - genetics; E3L; Female; Fundamental and applied biological sciences. Psychology; Genes, Viral - genetics; Genes, Viral - immunology; Immune response; Immunity, Cellular - immunology; Interferons - pharmacology; Kinases; Laboratories; Mice; Mice, Inbred BALB C; Mice, Inbred C57BL; Mice, SCID; Microbiology; Mutation; Mutation - genetics; Mutation - immunology; Neutralization Tests; Pathogens; Poxvirus; Rabbits; Smallpox; Smallpox vaccine; Spleen - cytology; Spleen - immunology; Vaccines; Vaccines, antisera, therapeutical immunoglobulins and monoclonal antibodies (general aspects); Vaccines, Attenuated - administration & dosage; Vaccines, Attenuated - genetics; Vaccines, Attenuated - immunology; Vaccinia; Vaccinia - immunology; Vaccinia - prevention & control; Vaccinia virus; Vaccinia virus - genetics; Viral Vaccines - administration & dosage; Viral Vaccines - genetics; Viral Vaccines - immunology; Virus Replication
• ISSN: 0264-410X; 1873-2518
• DOI: 10.1016/j.vaccine.2008.03.044

Summary In this study, we evaluated the efficacy of vaccinia virus (VACV) containing mutations in the E3L virulence gene to protect mice against a lethal poxvirus challenge after vaccination by scarification. VACV strains with mutations in the E3L gene had significantly decreased pathogenicity, even in immune deficient mice, yet retained the ability to produce a potent Th1-dominated immune response in mice after vaccination by scarification, while protecting against challenge with wild type, pathogenic VACV. Initial experiments were done using the mouse-adapted, neurovirulent Western Reserve (WR) strain of vaccinia virus. Testing of the full E3L deletion mutation in the Copenhagen and NYCBH strains of VACV, which are more appropriate for use in humans, produced similar results. These results suggest that highly attenuated strains of VACV containing mutations in E3L have the potential for use as scarification administered vaccines.