DNA Vaccines Encoding Viral Glycoproteins Induce Nonspecific Immunity and Mx Protein Synthesis in Fish

Abstract

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.Antiviral DNA vaccines carrying a gene for a major antigenic viral protein have received considerable attention as a new approach to vaccine development, especially when traditional vaccines have failed. They offer the advantage of mimicking a viral infection, resulting in host production of a single viral protein that is correctly folded and modified, and eliciting both cellular and humoral immune responses (9, 48). DNA vaccines have been developed for a wide variety of viruses, including influenza virus (14, 46), human immunodeficiency virus (7,15,42), rabies virus (38), hepatitis B virus (10), rubella virus (41), and foot-and-mouth disease virus (19). Genetic vaccines have also been developed for several other pathogens, including Mycoplasma pulmonis (29), Mycobacterium tuberculosis (34), Plasmodium yoelii (17), and Schistosoma japonicum (49).For fish viruses, DNA vaccines have been developed for infectious hematopoietic necrosis virus (IHNV) (2, 33) and viral hemorrhagic septicemia virus (6), both rhabdoviruses belonging to the Novirhabdovirus genus. Laboratory trials with fish indicate that these vaccines are considerably more effective in protecting fish from lethal challenge with homologous virus than either the traditional killed vaccine or the subunit vaccine we had developed previous...

The kinetics and protection of the antiviral state induced by recombinant iIFN1a in rainbow trout against infectious hematopoietic necrosis virus

“…Interestingly and significantly, an IHNV DNA vaccine could provide significant protection as soon as 4 d after intramuscular injection (LaPatra et al, 2001b). This early, nonspecific antiviral protection was shown to be associated with an induced type I IFN response in rainbow trout Oncorhynchus mykiss (Kim et al, 2000). The type I IFNs of rainbow trout have also been shown possess antiviral activities against viral hemorrhagic septicemia virus (VHSV) (Zou et al, 2007).…”

Review on current application of genomic biotechnologies to improve livestock and livestock products

“…It is important to express proteins of disease agents with the greatest possible similarity to the authentic molecule so that the proper immune response is induced when the proteins are used as a vaccine. Baculovirus expression systems are effective for properly modifying recombinant proteins so they are antigenically, immunogenically, and functionally similar to the native protein (Kim et al, 2000).…”

“…That success story is proof of the tremendous potential of vaccination and has led to the development of vaccines against almost all infectious agents affecting people and animals. The ultimate objective of vaccination is to induce an immune response that subsequently recognizes the infectious agent and fights off the disease (Kim et al, 2000).…”

The Protective Effect of Recombinant Glycoprotein Vaccine Against HIRRV Infection.

“…It has also been reported that an antigenic determinant of the glycoprotein gene of IHNV expressed as fusion protein with trpE protein of Escheri chia coli induced protective immunity (Gilmore et al, 1988). Recent studies on DNA vaccines for fish rhab dovirus glycoprotein also shown that the glycoprotein is sufficient to induce protective immunity against the cor responding virus and even other rhabdoviruses in the same genus (Corbeil et al, 1999;Kim et al, 2000).…”

“…However, a recent development in molecular biology has made it possible to produce a large amount of recombinant viral protein as a sub-unit vaccine that can be used for vacci nation by immersion or injection of individual fish (Munn, 1994;Lorenzen, 1999). In addition, viral genes cloned into an expression vector and introduced into fish tissue as DNA vaccines have been proved to be effective in in door experiments and small-scale field experiments (Corbeil et al, 1999;Kim et al, 2000).…”