[Pepper]

QUEBEC (CP) - Canada's pandemic flu vaccine maker is finalizing negotiations to import the seed strain needed to make a vaccine against the devastating H5N1 avian influenza virus, company officials have revealed.

ID Biomedical hopes to have the hybrid virus in the country before the holidays to begin work that could ultimately trim precious time off the vaccine production schedule when a flu pandemic is declared, company executives told The Canadian Press.

"It's all about shaving down time," chief executive officer Dr. Tony Holler said in an interview in Quebec City, where ID Biomedical's production plant is located.

The company will begin growing and amassing stocks of the virus, gaining experience working with what experts believe is currently the most likely candidate to spark the next influenza pandemic.

http://www.mytelus.com/news/article.do?pageID=cp_health_home&articleID=1791961

[CanadaSue]

People just please remember...

when H5N1 goes human to human & quite probably pandemic, chances are the genetic changes involved will mean this current seed strain vax will NOT WORK. The H in H5N1 is adapted to lock onto AVAIN DIGESTIVE cells. Yes we have cases where it's managed to latch on to human respiratory epithelial cells but for it to do this on a wide scale, the H MUST change significantly. That or those changes will likely mean the vax won't work - if MY UNDERSTANDING of how flu vax works is halfway accurate?

FrmlyZ - you're the pro here - HELP!

[CanadaSue]

Because I've comments on parts of it & I hate taking lines & paras out of context when there's important info to be gleaned & this article has plenty of meat; som very important points to note. I'll toss my comments in bold within the text or something. Think I can manage to do that without messing up - lol:

http://www.ctv.ca/servlet/ArticleNews/story/CTVNews/1102888326027_51/?hub=Health


***ID Biomedical to work on vaccine for H5N1 virus
HELEN BRANSWELL, Canadian Press

QUEBEC — Canada's pandemic flu vaccine maker is finalizing negotiations to import the seed strain needed to make a vaccine against the devastating H5N1 avian influenza virus, company officials have revealed. (Not quite. I still maintain the pandemic strain of H5N1 will be genetically different from this trial vax & thus, this vax may be useless AS a vax.)

ID Biomedical hopes to have the hybrid virus in the country before the holidays to begin work that could ultimately trim precious time off the vaccine production schedule when a flu pandemic is declared, company executives told The Canadian Press. (THat ONLY works if pandemic H5N1 matches this seed strain - unlikely.)

"It's all about shaving down time," chief executive officer Dr. Tony Holler said in an interview in Quebec City, where ID Biomedical's production plant is located.

The company will begin growing and amassing stocks of the virus, gaining experience working with what experts believe is currently the most likely candidate to spark the next influenza pandemic. (THis is what they're REALLY doning, gaining experience working with this new formulation.)

That viral seed bank could be used if, as expected, the federal government approves a roughly $20-million proposal to have ID Biomedical make trial lots of H5N1 vaccine. "The more experience collectively as an industry we have with these types of strains, the better off the whole world is," Holler said.

The World Health Organization has been encouraging vaccine manufacturers for months to start working with the H5N1 viral seed. To date only two -- Aventis Pasteur and Chiron Corp. -- have done so. They are producing trial vaccine batches for the U.S. National Institutes of Health. (We need EVERY flu vax company working on this - now.)

"It's important that vaccine manufacturers learn how to work with this material which is different than other influenza viruses and that they move through the regulatory process and find out where the bumps in that road might be and straighten them out," said WHO spokesman Dick Thompson.

Production of trial batches could substantially cut the time needed to produce the real thing if H5N1 does become a pandemic strain, explained Richard Holslag, ID Biomedical's general manager.

(They are using seed strain made with new technology - explained further down & yes, any problems with this TYPE of strain manufacture needs to be ironed out before we need to cran out millions of doses.)

The company will likely acquire the seed strain from Britain's National Institute for Biological Standards and Control, one of three labs which made a viral seed for the WHO earlier this year.

Using a technique called reverse genetics, scientists made a hybrid version of H5N1, merging the two surface proteins -- the hemagglutinin and the neuraminidase -- from the highly lethal virus with six internal genes from a human flu virus.

In the process, they plucked a string of amino acids responsible for H5N1's high pathogenicity from its hemagglutinin gene, a move designed to produce a vaccine that will activate an immune response without causing disease.

(The human flu virus used was a mild, research one. by simply extractng the amino acids necessary to stimulate an immune response) the chance of contracting H5N1 from the vac is nil. Because H5N1 is, so far, so lethal, the last thing they want is cases via vax. It's exceedingly rare that happens & results from older methods where virus is not thoroughly inacitivated.)

Holslag said ID Biomedical wants to have the viral seed in the Quebec plant before Christmas. "But if it is not before Christmas, it's early in January."

The work will be done in a small laboratory at the facility which Health Canada agrees meets Level 2-plus biosafety standards.

This work could trim days off the eventual vaccine production schedule, Holslag said. (Days ain't gonna do it, but bear ieth me...)

The company has identified ways to slash months off the time line, but those time savings will require up-front spending by the federal government.

In a presentation to Health Canada last month, ID Biomedical illustrated how a 7½-month production schedule could be cut to less than three months, if a trial H5N1 vaccine is made, tested and licensed now. Those times are based on a scenario where one dose of vaccine would be sufficient to protect a person.(Had to read this very carefully - there's not being deceptive but this is easily open to misinterpretation.. You'll see why.)



That trial work will tell authorities how large a dose humans need to gain protection from H5N1 and whether adjuvants - chemicals that boost the vaccine's potency - could be used to stretch initially limited supplies.

As well, they should indicate whether a single dose would confer protection or whether, as experts fear, a primer dose followed by one or two booster shots would be needed. (THey have to know this now. I'm now sure why they think we may need 2 doses each. That scenario wouold add to a pandemic nightmare & I'll try chase that down. Usually that's why we use adjuvents - to boost the effectiveness to the vax without needing more of the main ingredient itself.)

Unless adjuvants can be used, that latter scenario would mean at least 64 million doses -- produced at a rate of eight million doses a month -- would be required to protect 32 million Canadians.(Big problem here - you need about 4 months to even START big production runs of what's going to be injected into people. You need to get your eggs - they can only be about 10 says old, grow the virus for about 24 48 hours - I forget - then you have to extract & purify your vax, mic it up properly, do ylour quality assurance testing... Canada has toughly 32 million people. Maximum production of 8 million doses a months means at LEAST 8 months to get everyone 2 shots if that's what needed. It would be less - by the time many got to shot #2, the already be dead. BUt that would be offest by inevitable bad batches.)

If those dosing and formulations questions are answered in advance, if testing shows the vaccine is safe and if Health Canada regulators can complete licensing it, future batches of an H5N1 vaccine could piggy-back on that process.

That would significantly shorten the inevitable lag time between the start of a pandemic and the point when vaccine is available.(Bull, the process might be perfected bt they'd still need to wait for the strain to be identified, seed stock started & wait in line to get enough seed stock to start production. Minimum time - assuming 1 dose per & 2 per kid under 9, 6 months; no ifs, ands or buts.)

In order to make the trial lots of vaccine, ID Biomedical would have to upgrade a portion of its facility to higher biosafety standards.

"What we are talking about is, in effect, a small production line which will generate a product," Holslag said. "It will be a factory within a factory with its own licence." (Okay, but that works for the trials. For mass production you need to be building/upgrading & licencing larger scale facilities NOW.)

The federal government would have to pay for that upgrade, which would take five months for construction and some additional time for regulatory certification. That means that even if funding approval comes soon, trial vaccine wouldn't be available for testing until next September at the earliest.(I think that's too late. I'd prefer we be ready to test by spring.)

"When we talked with Health Canada in November ... we said: 'Well, if you decide on the first of December, we will have a batch ready at the end of August 2005,' " Holslag said.

"Each delay now is just a delay of that time."***

I've got more on a few other threads to come.

A lot of info is coming in awdully quickly for a Sunday. The urgency is doing nothing but increasing. Still as scary as it can be, I'd rather be readsing about who's doing what than worry no one is doing anything at all.

[y2kmisfit]

CS
I thought Avian flu vac. couldn't be made with eggs?
Am I wrong?

[CanadaSue]

It kills the blasted things dead before much virus is replicated - H5N1 is that lethal to chickens. So you're right, if they use the H5N1 genome - no joy. So they take a human strain flu - Puerto Rico 68 for example, strip out that H & N from that one & insert the H & N from the H5N1 virus. Because other genes in G5N1 contribute to the lethality to poultry, by not using them you eliminate that part of production problems. Sigh - here's where I REALLY with we han an influenza virologist aboard - lol.

Anyway once that's done, the THEORY is they can take the new, recombined virus & make vax seed strain from that. But it's new, so testing is required - why? We can never be certain until we see it what effects a recombinant may have. We don't compeltely understand all of a flu gene's functions. The basic human strain they used as a base is a real yawner but it's always possible it turns into a monster if you insert new genetic material - it's the same sort of issues we worry about with GE foods.

We have to make sure it's safe & also, does this new type of GE produced seed strain work the same way for dosages?

Already we're seeing that using cell cultures to grow flu virus is throwing up problems in terms of SOME vaccine tests - they're recording more adverse effects. I suspect much of that depends on what cell culture lines they use. It's all new stuff & while pandemic is frightening it's no excuse not to process with utmost caution.

[y2kmisfit]

so I'm assuming that because it can't be made with eggs, a new method to make vaccine will be needed and approved.
This would be why they are attempting this now, with a modified form of Avian flu, one that they know won't be the actual strain we will face. They must first find a method to make an Avian vaccine, and get that procedure approved. Then that step in the process will be eliminated when the real thing shows up.
Also, since it will be a totally new method of production, a new type of factory (lab) will need to be created (more time).
Does this make sense?

[CanadaSue]

The GE strain CAN be incubated in eggs which is exactly what they plan on doing. It was the seed strain which uses new methodology & I'm not sure about regulatory approval there. The 'lab within a lab' thing has me puzzled. If they're making a new BSL2 lab for this new seed strain, what the heck BSL level have they been using to make human strain vaxes? I'd like to think that was already BSL2 but perhaps not - I'll check. Okay here's Health Canada's rules for influenza virus handling:

***Biosafety Level 2

Risk Group 2 infectious agents are pathogens that can cause human or animal disease but, under normal circumstances, are unlikely to be a serious hazard to laboratory workers, the community, livestock, or the environment (moderate individual risk, limited community risk). Laboratory exposures rarely cause infection leading to serious disease; effective treatment and preventive measures are available and the risk of spread is limited.

Risk Group 2 infectious agents include, for example: E. coli; many salmonella; some fungi like ringworm; California encephalitis viruses; human herpes simplex viruses; many influenza viruses; Transmissible Gastro-enteritis of swine; Mouse Hepatitis Virus; and a few parasites.

Facilities, equipment, and procedures required to contain risk group 2 organisms at Level 2: Laboratory separated from other activities, biohazard sign, room surfaces impervious and readily cleanable. Equipment should include an autoclave, certified HEPA filtered class I or II biological safety cabinet for organism manipulations, and personal protective equipment to include laboratory coats worn only in the laboratory, gloves worn when handling infected animals. All contaminated material to be properly decontaminated.***

http://www.ccac.ca/english/educat/Module12E/module12-15.html

So is this BSL2+ or what? I'll admit I'm confused. Because vaccine is made FROM virus, you'd think the production facilities are routinely run at BSL2 anyway. Unless for added safety, they're simply nesting a smaller lab within a lab - odd. My only other thought is this smaller lab may be able to step up to BSL3 if the company itself is eventually licenced to produce the GE strain itself. Counting on seed stock from only 3 labs in the world means big delays from the outset.

Yes to the rest of your qustions. They need to iron out any wrinkles that crop up with this new GE flu virus as seed stock strain. Better now than when it's too late to work around unexpected problems.

However, I don't see the time savings here. At least a week to identify & isolate the causative strain of pandemic flu - minimum several weeks to brew up enough seed stock to distribute to whoever is going to make vaccine, then 6 or more months in which to be producing substantive quantities of vaccine.

Substantive is a subjective word. With only about 6 companies making flu vax throughout the world, a year's production run still only voers less than 5% of the world's population - assuming no production problems anywhere, anytime. As we saw this year with Chiron & see often enough with different vaxes, different plants - problems do happen for different reason. I contend that with the increased urgency & stress of a pandemic flu situation we may see MORE problems - shortcuts taken, people being so tired and/or worried they make errors...

Anyway, I'm still puzzled & looking for clarification.

[FrmlyZ]

CS:

I have been busy. I don't know what the regulations are in Canada but I suspect they are the same as here. If a pathogen can be transmitted in an aerosol, it requires BL3 containment. You are probably correct that things made to this recombinant, seed strain, will not be effective against the actual disease; if it occurs. At least that is the present dogma. That has been the experience. Present work has involved expressing the important, antigenic genes in plants like sunflower or tobacco. So far this hasn't worked. The plants add decoration which changes the antigenic characteristics of the proteins.

Best Wishes,,,,,,

Z

[CanadaSue]

Handy to have our own resident 'person who knows what the behoozles he's talking about'. The best I could do here was extrapolare by reading from OTHER PEOPLES' work on other organiss, describing running into unexpected problems of the sort. It made sense in the case of flu. We 'know' now that some genes express more than once during the life cycle of an organism, either alone or in combination with other genes AND based on different factors. I think it would be grossly imprudent to not consider that with the flu genome.

[shalym]

Hey Sue and Z--

I have a question...If I remember correctly, this strain is not nearly as lethal to ducks and other birds. Why can't they just use duck eggs rather than chicken eggs to grow the vaccine?

Shari