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Potential of equine herpesvirus 1 as a vector for immunization
Sascha Trapp1, Jens von Einem, Helga Hofmann
1Department of Microbiology and Immunology, College of Veterinary Medicine, Cornell University, Ithaca, NY 14853, USA.
Journal of Virology
|April 14, 2005
Summary
Equine herpesvirus 1 (EHV-1) shows potential as a vaccine vector, efficiently transducing human and animal cells. This animal herpesvirus can be manipulated in E. coli and induces immune responses, overcoming common vector limitations.
Area of Science:
- Virology
- Immunology
- Biotechnology
Background:
- Viral vectors face challenges like pre-existing immunity, low efficiency, toxicity, and limited genetic capacity.
- Equine herpesvirus 1 (EHV-1) is an animal virus with potential for therapeutic applications.
Purpose of the Study:
- To evaluate EHV-1 as a novel viral vector for gene therapy and vaccination.
- To assess EHV-1's transduction efficiency in various human and animal cell types.
- To determine EHV-1's immunogenicity and potential to overcome pre-existing immunity.
Main Methods:
- Reconstitution of EHV-1 from viral DNA manipulated in Escherichia coli.
- Transduction of primary human immune cells (CD3+, CD4+, CD8+, CD11b+, CD19+) and human tumor cell lines (MeWo, Huh7, HeLa, 293T, H1299).
- Intranasal delivery of EHV-1 in mice to assess lung transgene expression.
- Immunization of mice with EHV-1 carrying the HIV-1 Pr55gag gene to evaluate immune response.
Main Results:
- Efficient transduction of diverse human cell types (13-70% depending on cell type) was achieved with reconstituted EHV-1.
- Intranasal EHV-1 administration resulted in significant transgene expression in mouse lungs.
- EHV-1 vaccination induced a Gag-specific CD8+ T cell response in mice.
- EHV-1 was not neutralized by human sera containing antibodies against common human herpesviruses.
Conclusions:
- EHV-1 demonstrates high transduction efficiency in various human and animal cells, making it a promising vaccine vector.
- The ability to manipulate EHV-1 in prokaryotic cells and its high DNA packaging capacity are significant advantages.
- EHV-1's lack of cross-neutralization with human herpesviruses suggests potential for overcoming pre-existing immunity in vaccine applications.