Potential of equine herpesvirus 1 as a vector for immunization.
Abstract: Key problems using viral vectors for vaccination and gene therapy are antivector immunity, low transduction efficiencies, acute toxicity, and limited capacity to package foreign genetic information. It could be demonstrated that animal and human cells were efficiently transduced with equine herpesvirus 1 (EHV-1) reconstituted from viral DNA maintained and manipulated in Escherichia coli. Between 13 and 23% of primary human CD3+, CD4+, CD8+, CD11b+, and CD19+ cells and more than 70% of CD4+ MT4 cells or various human tumor cell lines (MeWo, Huh7, HeLa, 293T, or H1299) could be transduced with one infectious unit of EHV-1 per cell. After intranasal instillation of EHV-1 into mice, efficient transgene expression in lungs was detectable. Successful immunization using EHV-1 was shown after delivery of the human immunodeficiency virus type 1 Pr55gag precursor by the induction of a Gag-specific CD8+ immune response in mice. Because EHV-1 was not neutralized by human sera containing high titers of antibodies directed against human herpesviruses 1 to 5, it is concluded that this animal herpesvirus has enormous potential as a vaccine vector, because it is able to efficiently transduce a variety of animal and human cells, has high DNA packaging capacity, and can conveniently be maintained and manipulated in prokaryotic cells.
Publication Date: 2005-04-14 PubMed ID: 15827159PubMed Central: PMC1082783DOI: 10.1128/JVI.79.9.5445-5454.2005Google Scholar: Lookup
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Summary
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This research article discusses the potential of equine herpesvirus 1 (EHV-1), a virus common among horses, for use as a delivery mechanism (or vector) for vaccines and gene therapy. The virus has notable properties like high transduction efficiency, high DNA packaging capacity, and resistance to immunity developed against common human herpesviruses which might make it a viable choice for such applications.
Background of the Study
- The researchers aimed to solve problems typically encountered in using viral vectors for vaccination and gene therapy which include anti-vector immunity, low transduction efficiencies, acute toxicity, and limited capacity to package foreign genetic information.
- Equine herpesvirus 1 (EHV-1) was selected for study due to its overall potential for overcoming these issues.
Methodology and Findings
- The team reconstituted EHV-1 from viral DNA maintained and manipulated in Escherichia coli, a type of bacteria commonly used in genetics research.
- An efficiency test showed that the EHV-1 transduced (entered and delivered its genetic material to) between 13% to 23% of several different primary human cell types, and over 70% of CD4+ MT4 cells or various human tumor cell lines.
- Transgene expression, the process by which the genetic information carried by the EHV-1 was activated in the host cell, was successfully detected in mice lungs after intranasal instillation of the virus.
- Successful immunization using EHV-1 as a vector was demonstrated through the delivery of a human immunodeficiency virus type 1 (HIV-1) Pr55gag precursor, followed by the induction of a Gag-specific CD8+ immune response in mice.
Implications of the Study
- Testing showed that EHV-1 was not neutralized by human sera containing high titers of antibodies resulting from existing immunity against human herpesviruses 1 to 5.
- This research suggests that EHV-1 can efficiently transduce a variety of animal and human cells, has high DNA packaging capacity, and can be maintained and manipulated in prokaryotic cells (like bacteria), making it a valuable candidate as a vector for vaccinations or gene therapy.
- The ability of EHV-1 to avoid neutralization by the immune response to other herpesviruses increases its potential effectiveness as a vector in the human population.
Cite This Article
APA
Trapp S, von Einem J, Hofmann H, Köstler J, Wild J, Wagner R, Beer M, Osterrieder N.
(2005).
Potential of equine herpesvirus 1 as a vector for immunization.
J Virol, 79(9), 5445-5454.
https://doi.org/10.1128/JVI.79.9.5445-5454.2005 Publication
Researcher Affiliations
- Department of Microbiology and Immunology, College of Veterinary Medicine, Cornell University, Ithaca, NY 14853, USA.
MeSH Terms
- Administration, Intranasal
- Animals
- Antibodies, Viral / immunology
- CD8-Positive T-Lymphocytes / immunology
- CD8-Positive T-Lymphocytes / virology
- Cattle
- Cell Line
- Cross Reactions
- Gene Products, gag / biosynthesis
- Gene Products, gag / genetics
- Genetic Vectors / genetics
- Genetic Vectors / immunology
- HIV Infections / immunology
- HIV Infections / prevention & control
- Herpesvirus 1, Equid / genetics
- Herpesvirus 1, Equid / immunology
- Horses
- Humans
- Immune Sera
- Immunity, Cellular
- Immunization
- Leukocytes, Mononuclear / virology
- Mice
- Mice, Inbred BALB C
- Mice, Inbred C57BL
- Protein Precursors / biosynthesis
- Protein Precursors / genetics
- Spleen / immunology
- Transduction, Genetic
- Vaccines, Synthetic / biosynthesis
- Vaccines, Synthetic / genetics
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