Vaccination experimental vaccines to protect salmonids against infe ction with ihnv have been the subject of research for more than 40 years with some showing promise in both laboratory and field trials when delivered by. Another method to improve dna vaccine immunogenicity is the inclusion of additional plasmids, or additional inserts in the same plasmid, encoding molecular adjuvants. Licensed dna vaccines against infectious hematopoietic necrosis virus ihnv volume. The principle behind a dna vaccine is that the antigen can be expressed directly by host cells in a way that simulates viral infection and invokes an immune response from the host. Department of animal health, basque institute for agricultural research and development, neikertecnalia, technological park of bizkaia, berreaga 1, derio, bizkaia, spain 48160. The dna prime can also modulate the type of immune response 39 observed following the heterologous boost, in comparison with the booster vaccine alone 32, 40 35. Infectious hematopoietic necrosis virus ihnv was developed as a vector to aid the construction of vaccines against viral diseases such as viral hemorrhagic septicemia virus, spring viremia of. Ihnv isolates can be grouped into three genetic types, which are. Liu, in encyclopedia of immunology second edition, 1998. An influenza dna vaccine formulated in the lipid compound vaxfectin vical induced protective antibody titers and tcell responses in many subjects. West nile shot for horses is first licensed dna vaccine. Dna vaccine provided substantial protection of small fish.
Whodnadraft26 july 2019 page 3 of 39 1 2 guidelines for assuring the quality, safety, and efficacy of dna vaccines 3 4 5 introduction 6 7 background 8 9 purpose and scope 10 11 terminology 12 general considerations 14 15 part a. Product development for vaccines advisory committee pdvac. The relative efficacy of various routes of immunisation with pihnvwg was evaluated using 1. Licensed dna vaccines against infectious hematopoietic.
Ep21511a1 ep07856163a ep07856163a ep21511a1 ep 21511 a1 ep21511 a1 ep 21511a1 ep 07856163 a ep07856163 a ep 07856163a ep 07856163 a ep07856163 a ep 07856163a ep 21511 a1 ep21511 a1 ep 21511a1 authority ep european patent office prior art keywords characterized vaccine plasmid according vp2 prior art date 20061222 legal status the. Fish vaccines have been formulated from killed or attenuated pathogens, recombinant viral proteins or peptides, and most recently, plasmid dna encoding. Development of a suicidal dna vaccine for infectious hematopoietic necrosis virus ihnv. Human trials testing dna vaccines against influenza virus, malaria, hepatitis b virus, hiv, herpes simplex virus, colon cancer, and cutaneous tcell. Dna vaccines may be used in settings other than the prevention of disease in humans. M for monitoring the persistence of luciferase luc expression after induction of apoptosis. There is currently no commercially available vaccine for ihnv. The resultant dna vaccine microparticles were granulated with regular fish feed and given to fish to investigate the efficacy of the delivery system in providing protection against ihnv, and to demonstrate the ease of administration in fish. Infection with infectious haematopoietic necrosis virus 2.
However, none has focused on the diagnosis and vaccine. In 2005, apexihn novartiselanco became the first dna vaccine licensed for commercial use in aquaculture for protection of atlantic salmon against infectious hematopoietic necrosis virus ihnv. Changes to the insert or vector if the dna sequence of the insert gene andor backbone vector of a dna vaccine are. Lifetidesw5, an electroporationdelivered dna plasmid expressing porcine growth.
Bivalent dna vaccine induces significant immune responses. The target ihnv g gene was expressed in several organs of the vaccinated fish. Oct 24, 2017 recently in 2016, the european medicines agency ema recommended granting a marketing authorization in the eu for clynav, a dna vaccine against salmon pancreas disease salmonid alphavirus. Canada, an affiliate of novartis, was cleared for marketing by. Recently, an ihnv dna vaccine encoding the g protein of the j genotype was found to be effective against a wide range of ihnv strains by eliciting strong neutralizing antibody responses and upregulation of mx1 gene, an ifninducible antiviral effector xu et al. When the dna vaccine is administered to a patient, the machinery in their cells makes a viral or bacterial protein which their immune system. Dna vaccines is a major updated and enhancement of the first edition. A dna vaccine pirf1ag containing the promoter regions upstream of the rainbow trout irf1a gene driven the expression of the ihnv glycoprotein previously conferred a high level of protection against an ihnv challenge when administered by intramuscular injection. Pgacoated complex to pubm, a melanoma dna vaccine, noticeably impeded the growth and metastasis of a melanoma cell line, b16f10 cells. An oral dna vaccine against infectious haematopoietic necrosis virus ihnv encapsulated in alginate. Although very effective in protecting fish against ihnv, only one dna vaccine has been approved to date for use in canada. The centers for disease control and prevention cdc said the vaccine is the worlds first licensed dna vaccine one that uses small pieces of the target viruss genetic material instead of using a.
The first clinical trail, initiated to monitor the safety and efficacy of a dna vaccine against hiv1 infection, demonstrated that dna plasmid vaccines were safe and were capable of inducing detectable immune cellular and antibody responses 4042. Dna vaccination is a technique for protecting against disease by injection with genetically engineered plasmid containing the dna sequence encoding the antigens against which an immune response is sought so cells directly produce an antibody, producing a protective immunological response. Guidelines for assuring the quality, safety, and efficacy. Guidelines on manufacturing and control of dna vaccines 16 17 part b. This is similar to genscripts dna immunization technology which is a powerful tool that aids in custom antibody production against membrane proteins, other. There is an effective dna vaccine used in canada that is also li. Dna vaccine against west nile virus was used to vaccinate wild condors in california. The current flu vaccine is an inactivated virus, fuller. Jul 21, 2005 cidrap news federal officials say a new west nile virus wnv vaccine for horses, licensed this week, represents a breakthrough that may lead to important benefits for human vaccine development. Jul 18, 2017 in a previous study 43, the minimal dose of 1. Product development for vaccines advisory committee.
Their safety in terms of adverse reactions after injection has been demonstrated in animal models 38, 39 as well as in human clinical trials. As demonstrated in the field trials, a single dose of the. Our lab has developed a glycoprotein based dna vaccine for rainbow trout against infectious hematopoietic necrosis virus ihnv anderson, e. Process, use, method and formulation of disoxyribonucleic acid vaccine inclusion dna in nutritional compositions for animal in culture, particularly in fishery systems. Pdf development of a suicidal dna vaccine for infectious. Dna vaccines encoding the glycoprotein genes of spring.
A recombinant dna vaccine to ihnv was prepared and tested in field trials at clear springs trout companys box canyon hatchery in buhl, idaho this year in phase iii of the project. Generally, dna vaccines induce both early and late immune responses in fish that may be protective against disease. Infectious hematopoietic necrosis iowa state university. Abstractadministered by intramuscular injection, a dna vaccine pirf1ag containing the promoter regions upstream of the rainbow trout interferon regulatory factor 1a gene irf1a driven the expression of the infectious hematopoietic necrosis virus ihnv glycoprotein g elicited protective immune responses in rainbow trout oncorhynchus mykiss. Although effective, injection route is labour intensive and only practiced for highvalue species. Featuring applications which should be of great value in moving vaccines from research to clinic, this detailed volume includes sections on dna vaccine design and enhancement, delivery systems, production, purification, and quality. Cidrap news federal officials say a new west nile virus wnv vaccine for horses, licensed this week, represents a breakthrough that may lead to important benefits for human vaccine development. The aquaculture of salmonid fishes is a multibillion dollar industry with production over 3 million tons annually.
Hematopoietic necrosis virus ihnv dna vaccine apexihn developed by aqua health. The vaccine under consideration in these field trials consisted of lysed bacteria that contained a plasmid which expressed an antigenic portion of the ihnv glycoprotein. At three months postvaccination, specific immunity is clearly distinguished from the nonspecific immune response and good protection is observed only in animals vaccinated with a plasmid encoding the ihnv glycoprotein gene. The human immunodeficiency virus hiv vaccine is urgently needed to curtail the global aids epidemic. Pdf immune responses induced by candidate optimized hiv. This model has been instructive, in that in this system the mycobacterial protein is made by the mammalian host cell rather than by the organism. Although dna vaccines against ihnv and the related fish rhabdovirus, viral hemorrhagic septicaemia virus vhsv, have been shown to stimulate the production. Dna vaccines have potential advantages over conventional vaccines, including the ability to induce a. Pdf licensed dna vaccines against infectious hematopoietic. Once the dna reaches the tissue, the antigen is expressed in enough quantity to induce a potent and specific immune response.
The first dna vaccination of fish took place in 1996, when anderson et al. Recently in 2016, the european medicines agency ema recommended granting a marketing authorization in the eu for clynav, a dna vaccine against salmon pancreas disease salmonid alphavirus. Infectious hematopoietic necrosis virus ihnv, is a negativesense singlestranded, bulletshaped rna virus that is a member of the rhabdoviridae family, and from the genus novirhabdovirus. Methods and protocols, third edition explores innovative approaches and technologies used to design, deliver, and enhance the efficacy of dna vaccines. The excellent exceptions are dna vaccination against infectious hematopoietic necrosis virus ihnv at commercial level and against viral hemorrhagic septicemia virus vhsv at experimentalsmall scale level. Dna vaccines designed to target infectious hematopoietic necrosis virus ihnv are effective at protecting.
Investigators in professor deborah fullers lab have developed a dna vaccine that could lead to a universal, onedose flu vaccine. This procedure, known as a dna vaccine, is perhaps better described as a novel and powerful method for. Evaluation of a subunit vaccine to infectious hematopoietic. The most inducible of the type i ifn genes, by all stimuli tested, were rtifn3 and the short transcript form of rtifn1. West nile shot for horses is first licensed dna vaccine cidrap. The oral dna vaccine induced immune responses and protection in a dosedependent manner. Dna plasmid carrying a proteincoding gene that transfects cells in vivo albeit at a low efficiency and expresses an antigen causing an immune response 3. Guidelines for assuring the quality, safety, and efficacy of. A promising strategy to increase the dna vaccine efficacy, against other viral diseases, is to target the construct andtransgene to antigen presenting cells.
Three groups of trial participants 21 healthy hiv1negative adult volunteers were vaccinated four times with. Gene expression of rtifng1 and rtifng2 was highly upregulated by ihnv infection and dna vaccination but rtifng2 was induced to a greater. A dna vaccine against infectious haematopoietic necrosis virus ihnv is effective at protecting rainbow trout, oncorhynchus mykiss, against disease, but intramuscular injection is required and makes the vaccine impractical for use in the freshwater rainbow trout farming industry. An oral dna vaccine against infectious haematopoietic. The disease may be referred to by a number of other names such as chinook salmon disease, coleman. The vaccine is composed of the bacterial plasmid pcdna3 and the complete gene sequence for the glycoprotein of ihnv. Neeraj kumar,avtar, students jitender mehla research scholar,ndri and dr. However, despite many promising results in mice models, the majority of the dna vaccines tested in. It is in the same virus family as the rabies virus. Licensed dna vaccines against infectious hematopoietic necrosis virus ihnv. Recombinant subunit and dna vaccines dozens of vaccine formulations tested did not work via immersion delivery.
Field tests of most effective recombinant vaccine the three bestperforming subunitdna vaccines determined to be most efficacious in subobjective. Ihnv dna vaccine apexihn, novartis, containing a cmv promoter driving expression of the ihnv g gene, approved for commercialization in july 2005 by the canadian food inspection agency, veterinary biologist and biotechnology division. These three vaccines are planned to be used in field trials in the latter part of 1998 or the early part of 1999. Ihnv dna vaccine control mock dna vaccine ihnv g ucif eras pihnvwg pluc signs of ihn development of a novel vaccine for ihn ihn virus is a severe pathogen of salmon and trout that causes epidemics with 2090% mortality. Food and drug administration fda approved polymer that. Dna vaccines designed to target infectious hematopoietic necrosis. Ihnv isolates can be grouped into three genetic types, which are correlated mainly with geographic regions.
May 05, 2020 human trials testing dna vaccines against influenza virus, malaria, hepatitis b virus, hiv, herpes simplex virus, colon cancer, and cutaneous tcell lymphoma are underway and have only just begun. Oral dna vaccination of rainbow trout, oncorhynchus mykiss. Guidance for industry food and drug administration. Licensed dna vaccines against infectious hematopoietic necrosis. A dna vaccine uses a gene from a virus or bacteria to stimulate the immune system. Purified plasmid dna containing an antigens coding sequences and the necessary regulatory elements to expres them is introduced into the tissue via intramuscular injection or particle bombardment. Feb 19, 2014 since then several trials have been performed for a wide variety of fish species and pathogens and in 2005 a vaccine against ihnv infection in salmonids apexihn, novartis animal health was also one of the first dna vaccine ever to be cleared for marketing by the canadian food inspection agency. A decade later, recombinant dna technologywhich enables dna from two or more sources to be combinedwas harnessed to develop the first recombinant protein vaccine, the hepatitis b vaccine.
It causes the disease known as infectious hematopoietic necrosis in salmonid fish such as trout and salmon. Dna vaccination is a novel approach for inducing an immune response. Fish dna vaccine against infectious hematopoietic necrosis. Pdf the road to licensure of a dna vaccine researchgate. Methods and protocols, third edition explores innovative approaches and technologies used to design, deliver, and enhance the efficacy of dna vaccines featuring applications which should be of great value in moving vaccines from research to clinic, this detailed volume includes sections on dna vaccine design and enhancement, delivery systems, production, purification, and. Also developed is another suicidal construct pcmvlucpmt. The vaccine antigen is a hepatitis b virus protein produced by yeast cells into which the genetic code for the viral protein has been inserted. As would occur during a normal viral infection, the. Transmission potential of infectious hematopoietic necrosis virus in. In other cases, robust responses to the dna vaccine alone can be observed 26. Caused by the rhabdovirus, infectious haematopoietic necrosis virus ihnv, the principal clinical and economic consequences of. Sood, senior scientist,ndri,karnal contents introduction history dna vaccines vs traditional vaccines how dna vaccine is made methods of delivery how dna vaccine works advantages disadvantages current clinical trials safety issues future of dna vaccines conclusion references introduction dna. When the dna vaccine is administered to a patient, the machinery in their cells makes a viral or bacterial protein which their immune system recognises as being foreign to the body. Infectious hematopoietic necrosis is caused by infectious hematopoietic necrosis virus ihnv, a member of the genus novirhabdovirus and family rhabdoviridae.
Although vaccines against ihnv and ipnv have been commercialized in several countries, outbreaks of ipnv and ihnv are still a major problem. Currently, there is no effective treatment for ihnv infected fishes. However, infectious hematopoietic necrosis virus ihnv, which infects and kills salmon and trout, significantly reduces the revenue of the salmon farming industry. A dna vaccine pirf1ag against ihnn was orally administered to rainbow trout. Here, we report the findings from the phase i clinical trial of a candidate multigene hiv1 clade a dna vaccine and demonstrate the induction of hiv1specific immune responses. The centers for disease control and prevention cdc said the vaccine is the worlds first licensed dna vaccine one that uses small pieces of the target viruss genetic material instead of using. The oral dna vaccine significantly reduced virus load in tissues of the vaccinated fish.
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