Abstract |
In order to evaluate the conditions for optimal expression and immunogenicity of varicella-zoster virus (VZV) proteins in a herpes simplex virus-1 (HSV-1) vector, we selected the VZV glycoprotein E (gE), encoded by ORF 68 and the VZV product of ORF 62, an immediate-early major tegument protein (IE62). Three HSV/VZV recombinants were generated: (1) VZV gE protein coding sequences along with the promoter region were inserted into the thymidine kinase (TK) gene of HSV-1 strain KOS; (2) VZV gE expressed from the HSV-1 ICP4 promoter was inserted into the glycoprotein C (gC) gene of HSV-1 strain F; and (3) VZV IE62 protein coding sequences under the control of the HSV-1 ICP4 promoter were inserted into the gC gene of HSV-1 strain F. Immunoblot analysis and immunoperoxidase staining of infected cell monolayers demonstrated vector expression of VZV proteins. Following intracranial inoculation in mice, both VZV gE-HSV (TK) and VZV IE62-HSV (gC) induced an IgG response against VZV gE or VZV IE62. When tested in cytotoxicity assays using T-lymphocytes from VZV immune human donors, the range of precursor frequencies for T-lymphocytes that recognized VZV gE or VZV IE62 was similar whether these proteins were expressed by HSV-1 or a vaccinia vector. These experiments demonstrate that HSV-1 is a competent vector for expression of these VZV proteins and support the feasibility of engineering a combined vaccine for these closely related alpha-herpesviruses.
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Authors | P W Lowry, C M Koropchak, C Y Choi, E S Mocarski, E R Kern, P R Kinchington, A M Arvin |
Journal | Antiviral research
(Antiviral Res)
Vol. 33
Issue 3
Pg. 187-200
(Feb 1997)
ISSN: 0166-3542 [Print] Netherlands |
PMID | 9037375
(Publication Type: Journal Article, Research Support, U.S. Gov't, P.H.S.)
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Chemical References |
- Antigens, Viral
- Antiviral Agents
- IE62 protein, Human herpesvirus 3
- Immediate-Early Proteins
- Recombinant Fusion Proteins
- Trans-Activators
- Viral Envelope Proteins
- glycoprotein E, varicella-zoster virus
- Acyclovir
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Topics |
- Acyclovir
(pharmacology)
- Animals
- Antigens, Viral
(biosynthesis, genetics, immunology)
- Antiviral Agents
(pharmacology)
- Blotting, Southern
- Chlorocebus aethiops
- Cytotoxicity Tests, Immunologic
- Genetic Vectors
- Guinea Pigs
- Herpes Simplex
(immunology, physiopathology, virology)
- Herpesvirus 1, Human
(drug effects, genetics, isolation & purification, pathogenicity)
- Herpesvirus 3, Human
(genetics, immunology)
- Humans
- Immediate-Early Proteins
(biosynthesis, genetics, immunology)
- Immunoblotting
- Mice
- Mice, Inbred BALB C
- Recombinant Fusion Proteins
(biosynthesis, genetics, immunology)
- Recombination, Genetic
- T-Lymphocytes, Cytotoxic
(immunology)
- Trans-Activators
(biosynthesis, genetics, immunology)
- Vero Cells
- Viral Envelope Proteins
(biosynthesis, genetics, immunology)
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