Properties of a herpes simplex virus multiple immediate-early gene-deleted recombinant as a vaccine vector

Journal Article · Sat Jan 20 04:00:00 EST 2007 · Virology

DOI:https://doi.org/10.1016/j.virol.2006.08.015· OSTI ID:20850589

Watanabe, Daisuke ^[1]; Brockman, Mark A ^[1]; Ndung'u, Thumbi ^[1]; Mathews, Lydia ^[1]; Lucas, William T ^[1]; Murphy, Cynthia G ^[1]; Felber, Barbara K ^[2]; Pavlakis, George N ^[2]; Deluca, Neal A ^[3]; Knipe, David M ^[1]

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1. Department of Microbiology and Molecular Genetics, Harvard Medical School, 200 Longwood Avenue, Boston, MA 02115 (United States)
2. National Cancer Institute-Frederick, Frederick, MD 21702 (United States)
3. Department of Molecular Genetics and Biochemistry, University of Pittsburgh School of Medicine, Pittsburgh, PA 15261 (United States)

Herpes simplex virus (HSV) recombinants induce durable immune responses in rhesus macaques and mice and have induced partial protection in rhesus macaques against mucosal challenge with virulent simian immunodeficiency virus (SIV). In this study, we evaluated the properties of a new generation HSV vaccine vector, an HSV-1 multiple immediate-early (IE) gene deletion mutant virus, d106, which contains deletions in the ICP4, ICP27, ICP22, and ICP47 genes. Because several of the HSV IE genes have been implicated in immune evasion, inactivation of the genes encoding these proteins was expected to result in enhanced immunogenicity. The d106 virus expresses few HSV gene products and shows minimal cytopathic effect in cultured cells. When d106 was inoculated into mice, viral DNA accumulated at high levels in draining lymph nodes, consistent with an ability to transduce dendritic cells and activate their maturation and movement to lymph nodes. A d106 recombinant expressing Escherichia coli {beta}-galactosidase induced durable {beta}-gal-specific IgG and CD8{sup +} T cell responses in naive and HSV-immune mice. Finally, d106-based recombinants have been constructed that express simian immunodeficiency virus (SIV) gag, env, or a rev-tat-nef fusion protein for several days in cultured cells. Thus, d106 shows many of the properties desirable in a vaccine vector: limited expression of HSV gene products and cytopathogenicity, high level expression of transgenes, ability to induce durable immune responses, and an ability to transduce dendritic cells and induce their maturation and migration to lymph nodes.

• OSTI ID: 20850589
• Journal Information: Virology, Journal Name: Virology Journal Issue: 2 Vol. 357; ISSN VIRLAX; ISSN 0042-6822
• Country of Publication: United States
• Language: English

Related Subjects

60 APPLIED LIFE SCIENCES
DISEASE VECTORS
DNA
ESCHERICHIA COLI
GALACTOSIDASE
GENES
HERPES SIMPLEX
LYMPH NODES
MICE
MUTANTS
VACCINES
VIRUSES