Potential of equine herpesvirus 1 as a vector for immunization.
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.
Trapp
Sascha
S
Department of Microbiology and Immunology, College of Veterinary Medicine, Cornell University, Ithaca, NY 14853, USA.
von Einem
Jens
J
Hofmann
Helga
H
Köstler
Josef
J
Wild
Jens
J
Wagner
Ralf
R
Beer
Martin
M
Osterrieder
Nikolaus
N
D000281:Administration, Intranasal; D000818:Animals; D000914:Antibodies, Viral / Q000276:immunology; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology / Q000821:virology; D002417:Cattle; D002460:Cell Line; D003429:Cross Reactions; D015683:Gene Products, gag / Q000096:biosynthesis / Q000235:genetics; D005822:Genetic Vectors / Q000235:genetics / Q000276:immunology*; D015658:HIV Infections / Q000276:immunology / Q000517:prevention & control; D004861:Herpesvirus 1, Equid / Q000235:genetics / Q000276:immunology*; D006736:Horses; D006801:Humans; D007106:Immune Sera; D007111:Immunity, Cellular; D007114:Immunization; D007963:Leukocytes, Mononuclear / Q000821:virology; D051379:Mice; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D011498:Protein Precursors / Q000096:biosynthesis / Q000235:genetics; D013154:Spleen / Q000276:immunology; D014161:Transduction, Genetic; D014614:Vaccines, Synthetic / Q000096:biosynthesis / Q000235:genetics
D000914:Antibodies, Viral; D015683:Gene Products, gag; D007106:Immune Sera; D011498:Protein Precursors; D014614:Vaccines, Synthetic; C059767:p55 gag precursor protein, Human immunodeficiency virus 1