Fiskevaksiner og genteknologi – Internseminar - Bioteknologinemnda

Bioteknologinemnda: Internseminar 5. september 2001that is not simply a protein – it could be a modifiedprotein, modified naturally by the cell, or it couldbe very complex and involve lipids and things– it probably will not work. And that is one of thereasons why I say it is not a magic bullet. There is alimitation.Examples of experimental DNA vaccinesSome of these are in humans: You have malaria,mycoplasma, and a lot of viruses, such as rabies,influenza, AIDS, hepatitis. In fish there are a numberof experimental DNA vaccines, some for bacteria(Renibacterium, Aeromonas) and some for viruses(IHN, VHS, IPN, ISAV, SPDV).Safety issuesI will cover a number of safety issues. A lot of them haveto do with DNA vaccines in general, not necessarily fishvaccines. But the type of documentation is identicalfor all species, and of course have to be consideredalso with fish. The guidelines and documents that wehave to follow is:- A technical report by WHO (Technical report seriesNo. 878, 1998 – ”Guidelines for assuring the qualityof DNA vaccines).- A Note for Guidance from the European veterinaryauthority (Committee for Veterinary MedicinalProducts, CVMP), which is the major European sourcefor guidelines: ”DNA vaccines non-amplifiable ineukaryotic cells for veterinary use”.- An American-based Note for Guidance on DNAvaccines, probably the original Note for Guidance.One of the problems is that each note for guidance isa little bit different from the next. What the Americanswould like is a little different from what the Europeanswould like, and that makes things a little bit morecomplex, because then to have a totally documentedDNA vaccine, you have a lot more documentation todo.Basically, all the same principles apply toDNA vaccines as for any other vaccine in termsof documentation. So you don’t get by any easier.Everything that we have to document in order tosubmit an application to sell a “traditional” vaccinehas to be done for a DNA vaccine as well. And forthose of you who have never seen an applicationfor a vaccine, some of the vaccines that we haveapplied for permission to sell in Norway requires alot of documentation. So you don’t get any less workby developing DNA vaccines, as a matter of factyou get more, because you have additional safetyrequirements.Unfortunately, the guidelines for DNA vaccinesconsist of a mixture of the requirements found in all theexisting guidelines - the guidelines for recombinantDNA-derived vaccines, subunit vaccines, inactivatedviral vaccines, and live attenuated viral vaccines. Thiscreates a lot of confusion. The regulatory authoritiesand the people that designed the guidelines clearlyshow that basically we don’t really know where we sitwith DNA vaccines yet.These are safety requirements specific for DNAvaccines:- Distribution of DNA following vaccination: Wheredoes it end up in the organism, the fish or thehuman? The distribution is dose dependent and routedependent, and that has to be documented. You haveto use the most sensitive methods available, and dotime-course studies: What happens over a period oftime? If the DNA is everywhere in the body in thefirst half-hour but six months later, you can’t find itanywhere, that is something very important. If youstill find it after five years, that is something to worryabout.- Integration and production of tumours. Again,integration of the DNA into the genomic backgroundof the fish, the human, or the cow.- Reproductive toxicity. This covers the integrationof DNA into the genomes within the gonadal tissue,the sperm and eggs. Where does it end up, how longis it there?- Examination of immunological functions: Thereis an interest in knowing what is going on from animmunopathological reaction point of view: Whathappens? How is it working? The production of anti-DNA antibodies is specific for DNA vaccines, becauseit’s anti-DNA, but essentially no matter what vaccineyou use and what component you use, you still haveto look at the immunological response. You don’t wanta bad immunological response.- Cross-reaction. Does the DNA vaccine have an effecton normal functions within the cell? For example theproduction of cross-reactive antibodies.So in summary, for the interest of the Bioteknologinemndahere, I think the important points are:- Integration into the chromosome, either somaticand germline chromosomes; what the integrationPå ekskusjon til VESO Vikan AkvaVet.10