Vaccinia viruses with mutations in the E3L gene as potential replication-competent, attenuated vaccines: scarification vaccination.
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.
Jentarra
Garilyn M
GM
Graduate Program in Molecular and Cellular Biology, Arizona State University, United States.
Heck
Michael C
MC
Youn
Jin Won
JW
Kibler
Karen
K
Langland
Jeffrey O
JO
Baskin
Carole R
CR
Ananieva
Olga
O
Chang
Yung
Y
Jacobs
Bertram L
BL
D000281:Administration, Intranasal; D000818:Animals; D000914:Antibodies, Viral / Q000032:analysis / Q000096:biosynthesis; D000998:Antiviral Agents / Q000494:pharmacology; D002478:Cells, Cultured; D020552:Comet Assay; D006224:Cricetinae; D016207:Cytokines / Q000096:biosynthesis; D024882:Drug Resistance, Viral / Q000235:genetics; D005260:Female; D005814:Genes, Viral / Q000235:genetics / Q000276:immunology; D007111:Immunity, Cellular / Q000276:immunology; D007372:Interferons / Q000494:pharmacology; D051379:Mice; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D016513:Mice, SCID; D009154:Mutation / Q000235:genetics / Q000276:immunology; D009500:Neutralization Tests; D011817:Rabbits; D013154:Spleen / Q000166:cytology / Q000276:immunology; D014613:Vaccines, Attenuated / Q000008:administration & dosage / Q000235:genetics / Q000276:immunology; D014615:Vaccinia / Q000276:immunology* / Q000517:prevention & control*; D014616:Vaccinia virus / Q000235:genetics*; D014765:Viral Vaccines / Q000008:administration & dosage / Q000235:genetics* / Q000276:immunology; D014779:Virus Replication
D000914:Antibodies, Viral; D000998:Antiviral Agents; D016207:Cytokines; D014613:Vaccines, Attenuated; D014765:Viral Vaccines; D007372:Interferons