Anyone has experience of vaccine? - (Jul/06/2006 )

Why there is a shortage of vaccine every year? How long does it take to make the right vaccine after the outburst of new virus like new influenza virus?

Your question is somewhat difficult to answer. Vaccine production varies for every virus. I can answer you based on Influenza A though. Vaccine preparation is a year-round task. The WHO and the CDC work continuously to sample and sequence the strains of Influenza which are current threats around the world. This data is then used to decide which strains are to be included in the current vaccine. The vaccine traditionally consists of two strains of Influenza A and one of Influenza B. The Influenza virus must be grown in 10 day old embryonated chicken eggs and the parental viruses must be manipulated in a way that they are selected for in a "natural" sort of way. The means using antibody selection and manipulation and allowing nature to take its course. This can result in many rounds of infection/purification. Once the desired virus is obtained, it must be mass produced which is a lot of eggs. The virus must then be concentrated and inactivated. Through this whole process, every single little step and reagent must be recorded because it will go into humans. Research and design are typically handled by agencies such as the CDC, NIH and WHO. However, the actual production is turned over to pharmaceutical companies....and here comes the politics and money enter and subsequently your problems with underproduction, shortage, and overpricing. The most frustrating part is that there is a plasmid based system in which each plasmid encodes one of the 8 Influenza A genes. You can co-transfect these plasmids into cell culture and produce virus in 3-5 days (depending of the virus). Theoretically, you could make any needed changes quickly at the molecular level and then have your desired virus ready to go in a matter of weeks versus months. This would open a whole new door against the threat of deadly pandemic outbreaks as well. It is debatable though weither or not the FDA will ever approve the technique for vaccine production. The process is considered potentially dangerous because it passes through cell culture. In any case, hope this answers your question.

i recently read in new scientist

that from the date of the first strain of pandemic influenze being identified and an actually vaccine being produced and mass released to the public takes about 6-8 months

although smaller batches for emergency workers etc will be available earlier, most of the civilian population would have to wait 6 months for the "correct" vaccine

although their might be initial vaccinations with the current vaccines which might provide partial protection

I would push for DNA-based vaccination for that reason. It should be simple to R&D and manufacture than protein-based. Anyone here is working on this? how is the efficiency of this technology compared to the traditional one?

I've worked on it. The plamid based system can only be used for research purposes. Unless a new stratagey is develped, it is highly unlikely that the system will ever be used for vaccine purposes. The problem is that this system requires mammalian cell culture in order for the viruses to assemble and replicate. To put anything in humans that has passed through cell culture is very dangerous since it is difficult to guarantee that the cell line is not carrying any other viruses/pathogens or that components of the cell line are not being contributed to the viral harvest.

Maybe you are talking about recombinant viral vector as vaccine? I thought someone is working on pure plasmid DNA i.m. injection for vaccination. You get it from bacteria and you can certainly use defined medium to culture that. That would not have serious biohard issues. But I dont know how potent it is to stimulate immune responses and to what extend a suitable delivery system has been deveolped.

you mean stuff like this article from Pubmed? this stuff is related to my work on innate immunity, but I confess I don't know much about DNA vaccines beyond what's in the literature...I know that some types of microbial DNA elicit a pretty crazy innate response, with defensins and cytokines and such, but if you want to immunize by spiking a population of B-cells against the microbial DNA, I don't know how effective this approach can be

1: Helicobacter. 2006 Apr;11(2):113-22. Links
Mucosal immunization with a urease B DNA vaccine induces innate and cellular immune responses against Helicobacter pylori.Hatzifoti C, Roussel Y, Harris AG, Wren BW, Morrow JW, Bajaj-Elliott M.
Department of Immunology, St. Bartholomew's and the Royal London School of Medicine and Dentistry, London, UK. caterina.hatzifoti@paediatrics.ox.ac.uk

Close. More like this:
http://chi.ucsf.edu/vaccine/vaccines?page=vc-01-01

I think DNA based vaccines are much different because they are only expressing a single antigen or a combination of antigens. The 8-plasmid system for Influenza virus is much different though. Each of the 8 influenza genes are on a separate plasmid and they must all be co-transfected into mamalian cell culture in order to assemble and package a whole virus. There are currently 15 different HA variations and 9 NA variations (the two major surface antigens of the Influenza virus) that can be combined to produce very different strains of Influenza. The system would require manipulating these two plasmids in a "generic strain" background. There are other stratagies currently being researched though which use a platform (ex: woodchuck hepatitis virus core protein) to express multiple copies of the antigen/s (ex: M2). There is a similar problem with this in that you are introducing an additional protein from another virus.

Yes that's very true. Using 8 plsmids to generate attenuated virus is what we call reverse genetics, in which you end up with attenuated virus gerenated from transfecting mamlian cells 8 different plasmids each one contains different gene. people now use less than 8 plasmids to do that.
DNA based vaccine is something different, you clone your gene of interest into mamlian vector and purify that from bacteria and use it to immunize whatever you want. There are at least two approved DNA vaccines for animals (Horese and fish I think). Here you generate immune responses against the antigen encoded by you gene of interest.

Thanks