DNA vaccines encoding viral glycoproteins induce nonspecific immunity and Mx protein synthesis in fish.
Protective immunity by vaccination with plasmid DNA encoding a viral glycoprotein (G) has long been assumed to result from the induction of a specific immune response. We report here that the initial protection may be due to the induction of alpha/beta interferon, with long-term protection due to a specific response to the encoded viral G. DNA vaccines encoding the Gs of three serologically unrelated fish rhabdoviruses were used to vaccinate rainbow trout against a lethal challenge with infectious hematopoietic necrosis virus (IHNV). All three vaccines, each encoding the G gene of either IHNV (IHNV-G), snakehead rhabdovirus (SHRV) (SHRV-G), or spring viremia of carp virus (SVCV) (SVCV-G), elicited protective immunity against IHNV. Vaccinated fish were challenged at 30 or 70 days postvaccination with lethal doses of IHNV. At 30 days postvaccination, only 5% of fish that had received any of the G vaccines died, whereas more than 50% of the control fish succumbed to virus challenge. When fish were vaccinated and challenged at 70 days postvaccination, only 12% of the IHNV-G-vaccinated fish died compared to 68% for the SHRV-G- and 76% for the SVCV-G-vaccinated fish. Assays for trout Mx protein, an indicator of alpha/beta interferon induction, showed that only fish vaccinated with a G-containing plasmid produced high levels of Mx protein in the kidneys and liver. Interestingly, at day 7 after virus challenge, all of the fish vaccinated with the IHNV-G plasmid were negative for Mx, but the SHRV-G- and SVCV-G-vaccinated fish still showed detectable levels of Mx. These results suggest that DNA vaccines in fish induce an early, nonspecific antiviral protection mediated by an alpha/beta interferon and, later, a specific immune response.
Kim
C H
CH
Department of Microbiology, Center for Salmon Disease Research, Oregon State University, Corvallis, Oregon 97331, USA.
Johnson
M C
MC
Drennan
J D
JD
Simon
B E
BE
Thomann
E
E
Leong
J A
JA
D000595:Amino Acid Sequence; D000818:Animals; D000914:Antibodies, Viral / Q000097:blood / Q000276:immunology; D018899:CpG Islands; D005393:Fish Diseases / Q000276:immunology / Q000517:prevention & control / Q000821:virology; D019204:GTP-Binding Proteins; D006023:Glycoproteins / Q000235:genetics / Q000276:immunology*; D016898:Interferon-alpha / Q000096:biosynthesis / Q000276:immunology; D016899:Interferon-beta / Q000096:biosynthesis / Q000276:immunology; D008969:Molecular Sequence Data; D064547:Myxovirus Resistance Proteins; D009500:Neutralization Tests; D017686:Oncorhynchus mykiss; D010957:Plasmids / Q000235:genetics; D014176:Protein Biosynthesis; D012209:Rhabdoviridae / Q000145:classification / Q000235:genetics / Q000276:immunology*; D018353:Rhabdoviridae Infections / Q000276:immunology / Q000517:prevention & control / Q000662:veterinary / Q000821:virology; D017422:Sequence Analysis, DNA; D014611:Vaccination; D019444:Vaccines, DNA / Q000276:immunology*; D014764:Viral Proteins / Q000235:genetics / Q000276:immunology; D014765:Viral Vaccines / Q000276:immunology
D000914:Antibodies, Viral; D006023:Glycoproteins; D016898:Interferon-alpha; D064547:Myxovirus Resistance Proteins; D019444:Vaccines, DNA; D014764:Viral Proteins; D014765:Viral Vaccines; D016899:Interferon-beta; D019204:GTP-Binding Proteins