title: Development of a suicidal DNA vaccine for infectious hematopoietic necrosis virus (IHNV).
abstract: We developed a suicidal DNA vaccine (pIRF1A-G-pMT-M) for salmonid fish susceptible to Infectious Hematopoietic Necrosis Virus (IHNV). The suicidal vaccine consists of two operons: i) an inducible fish promoter, the interferon regulatory factor 1A promoter (pIRF1A), driving the expression of the IHNV viral glycoprotein (G) gene that induces protection, and ii) a ZnCl(2) inducible fish promoter, the metallothionein promoter (pMT), driving the expression of the IHNV matrix (M) protein that induces apoptosis. The vaccine induces an immune response to the G protein and then induces the cell to undergo apoptosis to eliminate the DNA vaccine-containing cell. Also developed is another suicidal construct (pCMV-luc-pMT-M) for monitoring the persistence of luciferase (luc) expression after induction of apoptosis. In this study, we evaluated the inducibility of the MT promoter with ZnCl(2) and the capacity of cells transfected with the suicidal vector pCMV-luc-pMT-M to undergo apoptosis after ZnCl(2) addition. We also demonstrated the protective immunity elicited by the suicidal DNA vaccine pIRF1A-G-pMT-M, the survival of fish after treatment with ZnCl(2), and the elimination of the suicidal vector in fish after ZnCl(2) treatment.
authors.affiliation: Department of Microbiology, Oregon State University, 220 Nash Hall, Corvallis, OR 97330, USA. malonso@neiker.net
authors.forename: Marta
authors.initials: M
authors.lastname: Alonso
authors.forename: Peter P
authors.initials: PP
authors.lastname: Chiou
authors.forename: Jo-Ann
authors.initials: JA
authors.lastname: Leong
mesh_terms: D000818:Animals; D017209:Apoptosis / Q000276:immunology*; D002460:Cell Line; D002712:Chlorides / Q000494:pharmacology / Q000633:toxicity; D005393:Fish Diseases / Q000401:mortality / Q000517:prevention & control*; D005786:Gene Expression Regulation / Q000187:drug effects; D029142:Infectious hematopoietic necrosis virus / Q000276:immunology*; D008156:Luciferases / Q000235:genetics / Q000378:metabolism; D008668:Metallothionein / Q000235:genetics; D017686:Oncorhynchus mykiss / Q000276:immunology*; D011401:Promoter Regions, Genetic / Q000235:genetics / Q000276:immunology; D018353:Rhabdoviridae Infections / Q000401:mortality / Q000517:prevention & control / Q000662:veterinary*; D016019:Survival Analysis; D014162:Transfection; D019444:Vaccines, DNA / Q000276:immunology*; D017967:Zinc Compounds / Q000494:pharmacology / Q000633:toxicity
chemical_list: D002712:Chlorides; D019444:Vaccines, DNA; D017967:Zinc Compounds; C016837:zinc chloride; D008668:Metallothionein; D008156:Luciferases