From Flu Wiki 2

Forum: Vaccination Strategies for H 5 N 1 Pandemic Part II

09 June 2006

BroncoBillat 01:35

Continued from here.


Original post from anon_22 – at 10:13:

It’s time to attempt a summary of the different considerations for vaccination strategies.

With the current state of science, vaccines are still the best bet for influenza control. However, there are numerous considerations such as:

1) finding the right antigen 2) efficacy 3) antigen sparing strategy 4) pre-pandemic vs pandemic vaccine 5) Safety 6) Regulatory issues 7) Production capacity 8) Delivery 9) Priority

clark – at 01:48

InfoLady – at 19:28 That is so cool that he sent you the article! Could you tell him that when I said “low tech”, I didn’t mean unprofessional-All safety precausions and procedures would be first class. I was thinking of using older and proven vaccine techniques that would be easier to set up in far flung places. The equipment would not be bleeding edge, that is all. Tell him that I live in New Zealand and we have no human vaccine making facility here - there are facilities for veterinary vaccines. I am interested in having local vaccine plants- particularly in my country- province and even my city.- but I was worried about the rest of the world as well. A well maintained older car will take you on a cross country trip just as well as a brand new one. You sacrifice comfort and convenience- In your Fathers opinion, is there any way that a little country like New Zealand could have it’s own vaccine plant/ plants??? Maybe making whole killed or attenuated virus vaccine? Thank him profusely for us!! kindest regards

InfoLadyat 10:17

Clark, when I have talked to my dad about this, he says the biggest barrier is not the facilities, but the people trained to do the work properly. Where will all these trained scientists and lab techs come from if they aren’t already in an area or a country?

Also, they would have to convert equipment to handle cell tissue culture vaccine production, in his opinion, if we are to create enough vaccine fast enough, even locally/regionally. One of the problems is that it looks like it will take much more vaccine per person (and perhaps two shots) to really immunize against this virus, unless some researcher can truly come up with a powerful adjuvent (that does not cause bad reactions in humans).

And right now, as far as he can tell, there is no coordinated, well-funded, research “blitz” to actually develop a vaccine that works — and to put in place the infrastructure to continue to develop the new versions that will be needed to deal with future mutations of the virus. Manufacturers, even if in place everywhere, can’t produce a vaccine that doesn’t exist.

Someone has to truly lead on this effort, and — in his opinion (and mine) no agency is really stepping up to the plate yet. Perhaps you could pressure some local/regional officials to push for more R & D on this — perhaps we all should!

anon_22 – at 17:07

InfoLady,

Thank you for explaining your dads ideas for us. The problems of needing higher dosage, personnel, conversion of facilities etc are phenomenal.

I don’t know how much ‘co-ordinating’ the WHO is doing, but certainly their special advisor on pandemic vaccines, Klaus Stohr, is a well respected scientist who has very detailed knowledge of all the ramifications and ongoing developments, and advises governments, often in rather blunt terms, not just on pandemic vaccines but the inadequacies of most countries pandemic prep. To borrow from someone else’s expression, he is one of the good guys. But of course they are limited in their influence as we know.

clark – at 17:28

Thanks Info lady- I have been writing to Dr. Mark Jacobs, who is heading New Zealands H5N1 response. He is at the NZ Ministry of Health. He reads my letters- but it is not like we are having a discussion. I’ll keep writing- and pass on your Fathers ideas! Tell him again how much his input is appreciated and ask him for MORE ideas. Vaccination is not my area, but it suddenly seems like the most important knowledge on Earth.

11 June 2006

clark – at 07:03

Info lady- any more comments from your Dad? I have thought about it- and plentiful and timely effective vaccinations seems like the only game in town. I don’t even think that full immunity should have to be the goal. My limited understanding is that the reason this virus is such a threat is that none of us have ever encountered anything remotely like it. We would bwe as lambs to the slaughter. Even an imperfectly matched (to the (if!)pandemic strain) H5N1 vaccine, would be beneficial- because our bodies would have been alerted to the existence to H5N1. We would get sick, and could even die- but we would have a much better chance.

Anyway, those seem to be Robert Websters thoughts on the matter.

Shelter in place is the right stategy till the vaccine arrives- but if the vaccine never arrives- SIP becomes less and less viable- this is assumning that the virus sticks around for awhile.

anon_22 – at 09:55

IF, and that’s a big if, we are absolutely sure a pandemic by H5N1 is going to happen, then a pre-pandemic vaccine producing partial immunity would make the most sense. But since no one, especially politicians, are willing to stick their neck out with such certainty, AND the cost of making a pre-pandemic vaccine for a sizeable portion of the population is prohibitive AND with the 1976 Swine Flu fiasco still fresh in memory, there is too little political will for it.

Webster is not the only one. John Oxford in the UK is also in favour of making a pre-pandemic vaccine for everyone NOW. His rationale is the same as Websters, that it may not prevent you from getting infected, but it will save your life.

Production needs to start NOW for a sizeable stockpile to make any difference. The ‘perfect’ vaccine will take years, and we cannot afford that. Having SOMETHING is better than having nothing.

I think if anybody is up for advocacy, that would be one worthwhile goal.

InfoLadyat 10:29

anon_22 — My father feels the same as Webster and Oxford in terms of creating some type of pre-pandemic vaccine, but acknowledges that this is unlikely to occur due to the need for, as he put it to me — lots and lots of scientists, facilities, and $$$$ put into the process. Not likely, given current political climates around the world. But certainly, as you say, a great place to focus advocacy.

One other issue is a lack of trained lab workers if we really need to gear up for massive production. Especially if we wait too long, and a pandemic does start, and we have even less people in the workforce. Where will the workers come from? Will they have been included in the initial “protection plan” for health workers and others? Is anyone thinking about this? (We might not want to just send all the bio-chem, virology, or other scientifically trained grad students home if campuses are closes, for example. Perhaps we should set up “clean areas” for them to live and work if necessary?)

anon_22 – at 11:11

“Where will the workers come from? Will they have been included in the initial “protection plan” for health workers and others?”

Well, the vaccine companies that I have spoken to plan on giving their employees the first batch.

Leo7 – at 17:39

From an article I just read called Influenza Report 2006 (sorry I couldn’t make it work for access, maybe a mod can help out)TPTB create mock vaccines of each strain they are able to tease out. Some discussion about making vaccine techniques and I got the feeling they feel there is a new discovery of producing vaccine on the horizon. (Monotremes DNA route discussed some) I haven’t seen it mentioned and it explains the basics in layman terms. I think it warrants a place in the archives. Forgive me all, if it’s a duplicate of another post. I found the references with summaries very informative as well.

NS1 – at 17:48

Leo7

Please Convert the long address to a short one at the link. Copy/paste the article URL address into the tinyurl conversion box. Press enter. Then copy / paste the resulting shortened link into your next post here.

Or

You can tell us where you got the info and someone will pursue it, I’m sure.

anon_22 – at 18:00

Mock vaccines http://www.influenzareport.com/ir/vaccines.htm

That’s exactly what is being done now. When companies say they have done such and such with H5N1 vaccine, they are using a strain provided by the WHO, currently the Vietnam one. This shortens the regulatory procedure needed for eventual substitution with the pandemic strain.

However, even with that, 2 different current estimates that I have seen give the following timescale:

from beginning of phase 4 alert to reference strain begin made available by WHO 20–80 days

start pandemic vaccine production under rapid regulatory approval > 3 months to first doses

anon_22 – at 18:02

or use the url markup this way [[ put url here | put link description here ]]

anon_22 – at 18:04

There are only 2 techniques different from the seasonal vaccine that have a chance of success measured in months and not years: whole virus vaccine, and intradermal applications. Everything else, we are talking about years.

clark – at 19:33

anon_22 – at 18:04- Could you tell us more about the “whole virus vaccine, and intradermal applications” please? Why will they take months? Why will the others take years? I am very interested.

InfoLady – at 10:29 “One other issue is a lack of trained lab workers if we really need to gear up for massive production. Especially if we wait too long, and a pandemic does start, and we have even less people in the workforce. Where will the workers come from? Will they have been included in the initial “protection plan” for health workers and others? Is anyone thinking about this? (We might not want to just send all the bio-chem, virology, or other scientifically trained grad students home if campuses are closes, for example. Perhaps we should set up “clean areas” for them to live and work if necessary?)”

I felt that info lady’s post bore repeating. There are thousands of senior and graduate students working in biohazard labs around the world as we speak. Maybe as a first step, they could be recruited- sort of like the Peace Corp or whatever. Maybe governments could pay their tuition fees in return for their help. One real advantage to using graduate students is that most of them will not have children yet- and very often their partners will be similar students. That removes many of the real problems of most workers- Their obligations to wives, husbands, children and elderly parents.

Tom DVM – at 19:40

Clark This has without doubt been an excellent discussion on all sides.

I think the point is here that we are once again not in control. At some point, the WHO, UN, sovereign health regulators and Governments will suddenly realize that their gamble failed, we are going to have a pandemic…

…If this occurs soon enough, they would have time to initiate a ‘war footing’. Others may correct me, but under war measures acts, I believe anyone can be gently forced to do what the Government requires…

…Your point about localized vaccine plants is a good one. If all the vaccine for the pandemic is made in one location (CHINA) and the vaccine does more damage then good…everyone who gets the vaccine will be in the same boat…

…If you spread the risk out to individual countries, then everyone can’t have bad vaccine and the overall risk would be less.

anon_22 – at 19:42

clark - I think most people underestimate the limitations of science.

I can’t tell you details of these processes cos I don’t know more than what I’m writing here. But those numbers/timescale are from vaccine companies as well as WHO pandemic vaccine development scientists. I’ve looked at various presentations I’ve seen from 2 different companies and 2 different WHO officials and they are very similar.

Anyhow, I’m going to this http://retroscreen.com/conference/programme.php later this month and hope to learn more. Will keep you posted.

Melanie – at 19:46

Y’all need to know that anon_22 has an almost endless ability to absorb conferences;>)

This one has a bunch of the “names” at it, so we’ll look for a full report when you return, anon.

anon_22 – at 19:50

Tom (& clark)

I just think that if we have a pandemic, we’ll be lucky to have any vaccine from anywhere. If China is the only country that’s made one, we’ll all have to take a chance.

Don’t get me wrong. I like people who can speculate creatively. But realistically the hurdles are huge, so I’m just hoping ANYBODY who can make anything is good.

Beggars can’t be choosers, I guess. :-)

anon_22 – at 19:51

“Y’all need to know that anon_22 has an almost endless ability to absorb conferences;>)”

I figure since I’m not an insider, that’s the closest I’m going to get for a fast-track education.

:-)

Tom DVM – at 20:02

annon 22. I think we have seen some pretty good examples already that several animal vaccines have created more problems than they solved.

Human vaccines, made in more of a panic, will be no different.

anon_22 – at 20:11

Tom,

I agree.

I still think we don’t have very many options.

Sorry to be so pessimistic. I try to look for good news everywhere but it’s kinda thin on the ground right now.

Tom DVM – at 20:22

annon 22. Agreed. I have no faith in the current technology. I believe only ten percent had an acceptable titre even with increased dose rates in the USA…and a reponse to a vaccine does not garuntee an effective protective immune response…

…if there is a solution it will have to be in new technologies and you and why probably would agree that time may be short.

On the intradermal vaccination. Children are a lot like animals that don’t understand language very well. You would know better then me how difficult this would be amongst several hundred squirming kids…I don’t envy you the job!! …and a lot of that intradermal vaccine is either going to go subcut or on the skin rather than in the skin.

I have a lot of questions that remain unanswered. I wish I could go to your conference…seems two the the top three will be there.

Ask them the tough questions and bring us back the answers. It will make for a very interesting thread of discussion…Thanks.

Leo7 – at 20:39

I’m thinking I’ve got some controls on cookies or something I need to check out. This is article is worth a perusal. Here’s the place. Tom agree the solution is in new technologies this article alludes too, also see references for more elaboration.

http://www.influenzareport.com/

clark – at 20:46

anon_22 – at 19:42- You will do us proud at the conference. Good luck and blow them away with our wiki brainstorming. thanks

clark – at 20:54

Thanks Leo7 – at 20:39- a very good link

“Production capacity

At present, the world has a production capacity of about 300 million trivalent influenza vaccines per year, most of which is produced in nine countries - Australia, Canada, France, Germany, Italy, Japan, the Netherlands, the United Kingdom, and the United States. In 2003, only 79 million doses were used outside of these countries and Western Europe. A further 13.8 million vaccines were produced and used locally in Hungary, Romania, and Russia (Fedson 2005).

Approximately 4–5 million doses of the live attenuated virus vaccine are produced per year.”

Why only 4–5 million doses of live attenuated? Does anyone know? Where is it made?

Tom DVM – at 21:09

Clark. I don’t know why anyone would be using a modified live influenza vaccine…makes no sense to me.

Tom DVM – at 21:14

Leo7.

Thanks that’s quite a reference!!

I don’t know how you and beehiver keep coming up with this stuff!!

anon_22 – at 21:21

I think the live attenuated vaccine is Flumist.

anon_22 – at 21:26

Some calculations for supply and demand:

current global capacity for trivalent vaccine (15ug x 3) is about 350M

If you use all of that capacity to make a monovalent vaccine at 15 ug dose, you get 1,050M doses.

But H5N1 is not very immunogenic. Without adjuvant, you need 90ug/dose, which means you get only 175M

With H5N1, there is also a problem with antigen yield during the process, and it can cut it down to 25% ie 44M

2 doses per person means you’ve got enough for 22M people/year. The world population is at 6 billion.

Go figure.

anon_22 – at 21:29

With adjuvant, you may be able to use 15ug instead of 90, although there is no successful results yet. That brings the total back up to 132M people per year.

If you use whole virus, some scientists say you MAY be able to get down to 7.5ug dose plus 1 dose would be sufficient. Which makes it approx 530M.

Still less than 1/10 of the world’s population in the first year, assuming optimal environment ie everything going according to best estimates.

anon_22 – at 21:30

That’s why whole virus is still the best bet.

Leo7 – at 21:43

While the numbers at first glance are bleak, there have been many ideas discussed here that would push that some-info ladies graduate students etc. My fear is pushing to fast and to hard and getting a vaccination that’s worse than 5 to 1. The thing that keeps me hopeful is whatever kicked out 5 to 1 and turned it on, can be the same thing that turns it off. Historically, we have more examples of that, instead of worse case scenario’s except for HIV which is at worst case to me. It’s also possible the labs are giving out low estimates in the vaccines numbers at normal speed-not ramped up speed. There is too much money floating around to put all faith in the numbers as reported. It hurts to write the previous sentence, but it needs to be written. I think the reports are grossly conservative.

anon_22 – at 21:48

Leo7,

“I think the reports are grossly conservative”

Well, we don’t know, do we? But there are only a limited number of vaccine companies and they are all keen on putting up a good show for their investors so I don’t see how they would want to under-report their capacity. If anything, it’s probably the other way round, and the figures include plants that are standing around and not in production. But operating a plant needs personnel, supplies etc. Unless it is cell culture, the supply of fertilized eggs is a major choke point.

clark – at 22:04

I think that under the circumstances, it is crazy to leave this to “market forces”. I honestly couldn’t care less what the vaccine companies’ bottom lines are- or what their return to shareholders are. It is irrelevant in the present circumstances. The whole point of having international political bodies, like the UN, WHO, EEU, NATO etc is to do what it is not appropriate for private enterprise to do. That is why Peace Keepers are soldiers, not soldiers of fortune.

We have our National, State, Provincial and Local governments- they need to get on the ball and do more than issue little advice pamphlets about preparing for hurricanes and “other natural disasters” (bird flu)

I want my New Zealand Government to start organizing local facilities for the production of a pre pandemic, pandemic and post pandemic vaccines.

clark – at 22:11

anon_22 – at 21:48 What is complicated about supplying fertilized eggs? All you need to add to a battery egg factory is a bunch of roosters. Or have I missed something?

I am sure the egg factories will be delighted. Chicken and egg consumption will decrease as the H5N1 gets closer- so there should be unlimited capacity - unless the virus gets lose in the egg factory. Egg factories are all over the place- I know of three or four around here. All the more reason to have many many vaccine factories - probably near the egg factories- and near the people who will be innoculated.

Tom DVM – at 22:27

annon 22. Did I read that right…with adjustments the world’s vaccine capacity is presently 22 MILLION treatments per year.

The best vaccine I used as a veterinarian was an intra-nasal killed vaccine. Its stimulation of a natural infection route seemed to more specifically stimulate the local immune responses better than intramuscular.

In my opinion, there are way to many if’s for this process to work in a panic…

…When the polio vaccine was designed by Dr. Saulk, the world was in the midst of an epidemic if not pandemic. Masssive supplies of vaccine were produced by one facility in a short period of time…

…it has been done before…of course as everyone tells me, we are so much more advanced then they were in 1918–1960 period.

Tom DVM – at 22:44

Just thought I would add one other piece of information as background. There have been three studies released in the past 16 months, two in the United States and one in Canada that all raise serious questions as to the efficacy of existing seasonal influenza vaccines…these problems of questionable effectiveness appear with recent H5N1 vaccine experiments to have been magnified by many multiples…

…You have to ask yourself a question. I have never seen a case in a free market economy where a vaccine company does not provide and saturate a market, in this case for flu vaccines…

…There is money to be made by making and selling these vaccines. The efficacy of these vaccines, in my opinion, is better described by the fact that there is only a market for 350 million doses worldwide…

…There must be a large percentage of the world that does not believe that these vaccines are even marginally effective and I believe the long-term studies back that conclusion up…

…There may be effective vaccines in the future but they will have to be based on a much improved knowledge of the transmissibility quotients for influenza and further research in modified vaccine technologies…

…for this pandemic, we are out of luck. With existing vaccines, it doesn’t matter a bit to my family whether there are 22 million treatments or 2.5 billion treatments, until I see more promising research data, my family won’t be getting any.

Leo7 – at 23:22

Tom,

For years they have been begging the general population to take vaccines, so that they could actually make more! People wouldn’t, so TPTB changed the recommendations; ie pregnant women, children, and some hospitals trying to make it mandatory for all hospital workers or no job! There is a reason why you’re hearing about a new vaccine almost evey month now. Vaccine production is market driven, plan and simple, and the market finally got what it wanted-no liability on their product. So, absolutely yes they will ramp it up now and Clark is right about the fertilized eggs—it ain’t rocket science. The problem is the intramuscular route, and it seems they are trying to get around it.

Average people have gotten a bad taste in their mouths with vaccinations due to the autism issue, and what happened to the first Gulf war vets. Everyone knows someone in one or both of this groups and mainstream science should’ve turned immediately to relevant research on these disputes. Instead they trotted out experts who said there was no correlation without providing research on it and the waters got muddied. Now, you see questions about the efficacy of yearly flu shots and what you have is a conundrum. If people stand up and demand this years flu shot—watch those numbers change fast.

My eighty year old neighbor refuses to take vaccinations and she hasn’t had any sickness and works out in her yard. She says they interrupt the natural cycle of immunity and it’s worked for her. So, how can I argue with a test driven product who walks two miles a day and beats me a bridge?

Tom DVM – at 23:47

Leo7. I’m with you on the intramuscular route. I always thought intramuscular vaccines work really well if the virus infects you by an intramuscular route…problem is that the most effective immune response like the most effective Government is local.

Intranasal vaccine is easy to give and mimics the natural route of infection and stimulates the immune system in the area that the virus infects.

I don’t think the lack of use is demand driven…I just don’t think they work and therefore cannot be sold…at least from what I’ve seen of the research…it doesn’t seem that we know enough about the basics of influenza to produce a good vaccine.

gharris – at 23:59

Anon-22 @ 18:00 “from beginning of phase 4 alert to reference strain begin made available by WHO 20–80 days” Didnt we decide that there wont BE a Phase 4 Alert? I wonder when they will decide to leap into action?

12 June 2006

Leo7 – at 00:05

Tom

A few years ago when FluMist came out we kept hearing from the ED nurses about people having severe asthmatic/allergic attacks from it. Several had to stay overnight for observation and it got a bad reputation among HCW. Intranasal vaccine also has some live virus which also has a history of contoversy and that’s why it’s killed now. But I agree with you it does seem the more natural route. FYI, I saw the nurse in my doctor’s office draw up the Flu shot in a Sub Q syringe to give to a woman who was grossly obese. I said something to the doctor and he went out to talk to her. I heard her explain to him the woman was scared of needles, so she used the little one. He looked as embarrassed as I felt by pointing out the error. He explained to her the shot was worthless unless it went IM, and she changed the needle. Just one more tidbit of why the flu shots may not work as expected.(needle length very important).

Tom DVM – at 08:05

How did H5N1 achieve efficient Human to Human transmisibility in 2006?

Well, H5N1 recombined with the modified-live vaccine strain that we were using in our vaccine at the time.

anon_22 – at 09:55

Actually, securing the supply of fertilized eggs is one big limiting factor. I don’t know the details but again this is a theme that comes up repeatedly when I speak to various people so there is probably some truth in that.

anon_22 – at 09:58

gharris,

“Anon-22 @ 18:00 “from beginning of phase 4 alert to reference strain begin made available by WHO 20–80 days” Didnt we decide that there wont BE a Phase 4 Alert? I wonder when they will decide to leap into action?”

By ‘we’ you mean fluwiki. :-) The WHO has not officially said that.

In any case this is from documents used to calculate the time to get a seed strain so if we don’t have phase 4 it will be phase 5 or 6 or whatever we want to call it. Just recognise it as the official start of a pandemic.

beehiver – at 09:59

Tom 08:05, exactly one of my primary concerns. Nucleic acids seem to have a talent for “swapping spit”, this is showing up in backfired genetically engineered products.

I would be incredibly scared to get a live H5N1 intranasal vaccine, or even partially killed. The nose has nerves that lead directly to the brain, and considering that H5N1 virus is sometimes neurotropic…well, need more be said…

Here is an advisory that was issued regarding use of veterinary DNA vaccines, and some of the issues surrounding those types of vaccines. Especially - page 3 covers some important concerns and is very readable, not too technical.

http://www.emea.eu.int/pdfs/vet/iwp/000798en.pdf

The Sarge – at 10:03

Anon_22

You are more right than maybe even you realize.

anon_22 – at 10:09

clark,

“I think that under the circumstances, it is crazy to leave this to “market forces”. I honestly couldn’t care less what the vaccine companies’ bottom lines are- or what their return to shareholders are. It is irrelevant in the present circumstances. The whole point of having international political bodies, like the UN, WHO, EEU, NATO etc is to do what it is not appropriate for private enterprise to do. That is why Peace Keepers are soldiers, not soldiers of fortune.”

It is not just market focus, by now. But the bottom line is it is the commercial entities that have the existing facilities. The WHO and at least some governments like the US and UK are kicking butt.

The problem is persuading them to come up with the money. If politicians can be persuaded by the voters that it is worth spending billions then we may see faster action. The biggest need for money is not research, but commitment to buy ie placing orders.

If governments are willing to actually put the money on the table and say here’s the money, make us x million doses asap, then the companies can ramp up production. They cannot justify taking on this much investment risk without solid orders. But governments are not willing to put the money down unless a) they see the pandemic as inevitable AND b) they are sure that particular vaccine works.

So we have a egg-and-chicken (an unfortunate but true analogy) situation, govt won’t buy without being sure of the need, companies won’t expand withous being sure the govt would buy.

“I want my New Zealand Government to start organizing local facilities for the production of a pre pandemic, pandemic and post pandemic vaccines.”

I don’t know how much NZ is doing, but if they do not already have the expertise, they will have to negotiate very hard with the companies to build plants there. You might want to ask explicit questions of your government to find out. Remember every country that can afford it is now doing the same thing ie trying to persuade vaccine companies to build on their soil.

anon_22 – at 10:10

Sarge.

“You are more right than maybe even you realize.”

Yes, my ego says so too. :-) Just kidding.

But which bit?

cactus az – at 10:52
 There are some folks at ASU (Arizona State Uni) who are working on developing a vaccine that will be cultured in vats,using samonella.If I knew how do a link I`d link to the article.

The article states that it takes 1–2 eggs per each dose of vaccine.

 And, aren`t the eggs used from chickens that are genetically thye same, and raised in almost sterile conditions? Not your free ranging hens.
anon_22 – at 11:34

cactus,

I don’t know about the one you mentioned but I’ve also seen at least with regards to H5N1 which requires large antigen doses we are looking at 1 egg per dose approximately.

The Sarge – at 13:32

Anon_22

The egg bit. If we are looking at (at 2 X 90 mcg antigen) - as many as 12, maybe more eggs per immunization. Yields for the annual trivalent vaccine are typically ~ 15 mcg/egg. we are reportedly getting something less than that with the H5N1 pandemic vaccine candidate. Start the math, considering that one particular breed of chicken is used as the layer for the vaccine. Healthy hens typically lay one egg roughly every 25 hours. Add up the numbers of chickens involved, and that the eggs need to be fertile and incubated for a very specific length of time pre- and post-innoculation. There’s a lot of commas in the resulting number.

anon_22 – at 14:10

So is 1 egg per 15 mcg for trivalent and less for H5N1 about right?

90 mcg x 2 per person means 12 eggs per person.

WOW! Holy smoke!

Tom DVM – at 14:15

annon22. It seems odd that under pandemic conditions we are going to rely on the one species most at risk to deliver us from evil…

…It doesn’t seem to matter at what angle we look at this does it?

anon_22 – at 14:19

“annon22. It seems odd that under pandemic conditions we are going to rely on the one species most at risk to deliver us from evil…”

That’s the irony of the situation, isn’t it?

Wasn’t there a movie once called ‘The Gods Must be Crazy’?

clark – at 18:33

Infolady, could you ask your father about the details of fertilized chicken’s eggs for making flu vaccine, please? In his opinion, how difficult would it be to ramp up production of the eggs? How important is the specific breed? How are the conditions different from an ordinary egg production facility- how sterile etc?. - free range would be the easiest way to make the eggs fertile. Fertilized eggs is very easy- factories go to great lengths and expense to keep eggs unfertilized. (chickens being chickens)

There are hundreds of millions (billions?) of chicks born each year- for rearing as meat or as layers. The facilities already exist to fertilize eggs and rear them to chicks. I still can not see the problem.

Tom, you are correct- we are relying on the chicken- the creature most vulnerable to H5N1. What can you do???

Tom DVM – at 19:35

Clark I agree and that’s the point. The powers that be have been running around telling everyone that mortality will be 2–7 million worldwide because we are so much more advanced then they were in the early part of the twentieth century…

…I’m not going to relist what I have said in the past about just how ‘flat out idiotic’ this claim is but Connaught labs in Canada, in response to Dr. Saulks polio vaccine, and faced with a worldwide pandemic of sorts, in a short period of time managed to produce all the vaccine that was needed. This was a public-private partnership and there is no reason the same couldn’t be accomplished today…as you have discussing in this thread long before I said anything.

So here we are relying on chickens to save us when the workers will probably give the chickens H5N1 and on top of that there has not been one piece of realistically promising news despite now three years of investigation into an H5N1 vaccine.

The question is not whether we will get the vaccine right for this pandemic…the question is will we get it right for the one after this pandemic…

…the first step to making things better is for them to ADMIT THEY HAVE A PROBLEM WITH EXISTING VACCINES AND ANTIVIRALS!! (Sorry)

clark – at 20:08

Tom DVM – at 19:35 You are correct- we do have a problem- and are response so far seems to be (1) “kill all of the local chickens”, (2) hand out Tamiflu. This is not an enduring stategy for the medium or long term. Even in the short term, it seems crude and doomed (Flu is not SARS or foot and mouth disease).

My understanding is that (1) we prepare to shelter in place - quarentine (2) Have antibiotic, rehydration solutions, herbal remedies, predisolone- acording to our own points of view. and (3) wait for the calvary to arrive- VACCINE.

(1) and (2) we can do ourselves with a bit of lateral thinking. We have decided that making our own vaccine in our basements is not a good idea. Probably making our own vaccine is not even a good idea if we do it in the garage or the shed.

Sooooo, we are going to have to wait for someone else to make the vaccine- and get it to us.

Tom DVM – at 20:15

Clark. The Calvary ain’t coming. All the horse got shot about twenty-five years ago!!

The only solution is the one you have been so wisely discussing. 1)a Local Effort ie: in country vaccine production or 2) a ‘war footing’ type effort, following the example set by Connaught Laboratories of Canada in the 1950′s with respect to Polio vaccine.

anon_22 – at 20:24

clark & Tom,

I just started another thread on MF59, which is the most likely proprietary adjuvant to be used for a pandemic vaccine.

Tom DVM – at 20:59

anon 22. Thanks.

clark – at 21:38

Tom, in your opinion, is there ANY way to manufacture vaccines and deliver vaccines that would impart a good level of immunity in the short to medium term? This is allowing for some bad events- like being dangerous for people with a suppressed immune system or causing localized swelling. I am not asking for something that is absolutely perfect-

Is it the adjuvants that is causing the problem- or the vaccine? Could we just make lots and lots and lots of straight whole virus vaccine and forget about the adjuvents. One thing you can say about H5N1, it shows a real propensity for vigorous growth on a variety of different mediums (species)- this is no shrinking violet. All we have to do is grow large amounts of this Beast, kill or cripple it- and spray it into peoples noses? or have I missed something? again.

Tom DVM – at 22:11

Clark No I don’t think you’ve missed anything. In principle, you grow the vaccine, make sure it is dead and then introduce it to the immune system, one way of another.

The best vaccine is delivered by Mother Nature…so another way this should be looked at is that if you are naturally infected with H5N1, you will probably have an 80% chance of surviving with absolutely no after-effects. You then wouldn’t be completely immune to another mutated strain but would probably have partial immunity probably better than anything you would get in a vaccine…

…All and all, not the worst odds I have ever seen. What do you think?

To be honest I would rather take my chances with Mother Nature than the Chinese Government or the Canadian Government, for that matter, with a vaccine without normal liability rules in place…

…Maybe we should all be in the vaccine business. We can sell ‘snake oil’ as well as the next guy!!

clark – at 22:24

Tom, how about a gold exploration company with a vaccine production subsiderary? We could float it on the Calgary Stock Exchange.

Seriously- Would getting infected naturally with a very low dose of virus, lead to no apparent infection or a lower grade infection and a bigger chance of recovery? You know all the stories of day care workers getting sick all the time- presumably because they are constantly getting exposed to massive loads of infectious bugs. Other people who are more solitary- rarely get sick- They are still exposed to the bugs- but typically much much lower doses.

Over time, by sheltering in place- and being exposed to small doses of H5N1 repeatedly through casual contact- a few million viri here and few million viri there- would we tend to develope an immunity over time?????

Tom DVM – at 22:53

Clark. I didn’t know that Calgary had a stock exchange.

I don’t think that vaccines are going to work…so they will create the worse of all worlds…a false sense of security.

At least if the vaccine is produced in New Zealand, those accountable will be close at hand which means they will automatically be more responsible, unlike others who will remain unnamed.

Unfortunately, skillful avoidance is the only way.

clark – at 23:03

Tom, if the virus is endemic- will skillful avoidance work? There must be some way to aquire some immunity with out finding out if you will live or die? It is like Russian Rulliet. The oldies with one bullet in the chamber- the youngies with two. How can we aquire some immunity? think everybody, there must be an answer

beehiver – at 23:04

Clark at 22:24. Boy, that’s a hard one. It would probably depend on whether the particular virus one was naturally infected with, was a super-replicator or not.

SCW AZ – at 23:08

Tom DVM – at 22:53 Clark. I didn’t know that Calgary had a stock exchange.

Calgary Stock Exchange is known for lots of oil and mining plays. Very loose controls, kind of like Las Vegas without the warm weather & flashing lights

Tom DVM – at 23:09

Clark. The bottom line is exactly what you and Infolady and NS1 started with in your thread. Several different vaccines produced in several different countries at the same time around the world.

New Zealand has the expertise to do it…it just hasn’t been done in some time due to Globablization and the merging and therefore eliminating the small companies.

It has been done before …google polio and Connaught Laboratories.

The nice thing about the disseminated production of vaccines is that some of them just might work and if you are the lucky one to recieve the one that does work, you will have at least partial immunity.

Tom DVM – at 23:11

SCW AZ. Thanks. I thought that was the Vancouver Stock Exchange but it must have moved to Calgary when I wasn’t looking.

Hurricane Alley RN – at 23:50

Can it be be said that Tom DVM is not a gambling man? Don’t blame him. The odds are not in our favor. Could it be said, “If BF doesn’t kill you, the vacine will.”

Another way to look at it. With the number of people taken by the flu, means more vaccine to go around. What an awful thought. gina

13 June 2006

clark – at 03:24

If getting sick with the flu imparts some immunity, then being exposed to killed or crippled virus should do the same thing. I just can not figure out why this is so difficult. I KNOW we can get fertilized chicken eggs. There is a chicken farm with 900,000 birds 15 kilometers from my house.

anon_22 – at 06:45

clark,

“If getting sick with the flu imparts some immunity, then being exposed to killed or crippled virus should do the same thing. I just can not figure out why this is so difficult.”

You’re trying to juggle getting INFECTED or GETTING NO IMMUNE RESPONSE. It’s like having your cake and eat it.

There’s no free luncch on this planet.

The Sarge – at 09:05

All -

There is an industrial base for producing eggs for vaccine production. It is smaller today than it was 25 years ago, most pharmaceutical makers having gotten out of the business for a plethora of reasons that we will leave alone for the moment. This base is insufficient to produce the amount of vaccine that is required to raise the level of herd immunity above a threshold where a pandemic virus is stopped in its tracks. I don’t know what that threshold is, but let’s say it is 80% (using the example of smallpox).

All phases of manufacture have to be expanded simultaneously. We can’t throw resources into expanding egg production without increasing the ability to innoculate, incubate and harvest the eggs; extract and purify the antigenic proteins and, bottle the vaccine. The vaccine must be maintained under cold chain. The problem we have is that the base is too small at this time, and considering that we may need as much as 12 times as much antigen per immunization as for the seasonal trivalent preparation, we are looking at an order of magnitude (times 10) increase in the manufacturing base. If we started now, we might accomplish this in 3–5 years with a MASSIVE building program.

The question is - will the bug give us that much time?

Tom DVM – at 09:09

Sarge. I have not way to tell for sure, but knowing Mother Nature the way I do in reference to disease, I don’t think so.

Medical Maven – at 09:16

Don’t forget guys, we humans probably need ten years of DITHERING “to and fro” before we begin the “3–5 year massive building program”. Build those bunkers and build them deep.

InfoLadyat 10:53

Clark and others — My dad does not think we should even waste our time with the chicken egg production route, pure and simple. The fact that H5N1 is so virulent in chickens is one reason; the others (production problems, etc.) have been well documented here. He says that tissue cell production is the way to go — requires a change for many current vaccine manufacturers, though, so that may be where the “bottleneck” is (and will be).

I do think if necessary that the “war footing” suggested by Tom DVM could work — large labs/production facilities could be contracted in public/private partnerships to accomplish this.

Too bad Salk has passed on. My dad always said Salk was one of the most creative and brilliant researchers he ever met, even when quite advanced in years.

Leo7 – at 15:42

Tom at 22:11:

Completely agree. If we dodge 5 to 1 do you think the companies will just naturally ease out of chicken egge production into cell cultures? So the next virus, slow manufacturing time won’t be an issue?

The Sarge – at 15:58

Leo7,

This is tangentially related to some things going on in other threads. First, we have to acknowledge that money makes the world go ‘round. Thus it is with vaccines - there has to be a market for the endeavor to truly be successful. Cell culture facilities are so fabulously expensive to build that manufacturers are looking to other methods to make their biologics, including transgenic plants (corn, tobacco, etc.)

I don’t pretend to have even the remotest idea of how to make the economics of the thing work. I suspect that we will need to greatly expand the numbers of folks who get a seasonal flu vaccine from where they are now. This would provide two benefits - One, there are fewer opportunities for a potential pandemic strain to meet and mate with an epidemic bug (reassortment, recombination -whatever). Two - the increased market helps support the truly gigantic investment in the technology and facilities. I think we need to have a realistic economic basis for this in the long run. If we are soley or even primarily dependent on the vagaries and capriciousness of government funding, the effort will never get off the ground or collapse in short order - my utterly unqualified opinion!

Leo7 – at 17:05

Sarge:

I’ve written several comments I’ve deleted. These companies are very rich, and in order to encourage them we have had to expand the guidelines for flu shots to pregnant women and children. I don’t agree with this, I’m sorry. It’s a bit like your company withholding money from your paycheck to pay for company expansion and you don’t get profit sharing. If they (all of big Pharma)truly believed in health care they would manufacture and give vaccines out for free as thanks to the millions of people who VOLUNTEER to bring their normal drug cash cows to prescription. Now, that would be true profit sharing.

Tom DVM – at 17:09

Leo7. Thanks. I think the big problem here is that regulators lead by the WHO and Governments lead by the UN, are convinced that we are somehow going to beat the bullet…therefore they don’t need to do anything constructive, just make it look like they are doing something constructive.

Sarge. The powers that be decided we needed an atomic bomb. Correct me if I am wrong, but I don’t think that process was driven by profit. Now, for the first time since 1942, we are in a similar threat position in respect to world population at risk. Is it not concievable that once again, using the example of Connaught Laboratories and Polio vaccine, that we could do it again, only this a peace time endeavour?

What do you think?

anon_22 – at 17:24

Tom,

“Sarge. The powers that be decided we needed an atomic bomb. Correct me if I am wrong, but I don’t think that process was driven by profit. Now, for the first time since 1942, we are in a similar threat position in respect to world population at risk. Is it not concievable that once again, using the example of Connaught Laboratories and Polio vaccine, that we could do it again, only this a peace time endeavour?”

It’s a worthwhile goal. Problem is that it will take too long and again need too much money.

Also, the atomic bomb happened because the goals of the scientist, military and the welfare of the nation happened to (sort of) coincide. We don’t have that here. I’ve been re-reading parts of the Vaccine A book today and feel really saddened about the close relationship between the military and commercial ventures and using public resources for private profit. It’s not a nice picture and picking your way through such stuff can be demoralizing and frustrating.

Leo7 – at 17:36

Anon 22 at 17:24

I’m trying to find my copy. It reminded me of the way experiments were done on prisoners and then we had social reform. Suddenly the soldiers, the ones who protect us, are the new fangled guinea pigs. I actually did puke. Then I read the ACHRE report that Bill Clinton made public—This experimentation on the military has been going on forever.

Leo7 – at 17:38

If anyone wants the ACHRE link it is here: http://www.eh.doe.gov/ohre/roadmap/achre/overpt1.html

The Sarge – at 17:44

Tom,

If (and it’s a big IF) we could get the political leadership to buy into the war time analogy that you have set forth (and I think we agree that emerging/re-emerging disease is as big a threat as has ever been)- it could work. The atomic program had a constant foil to justify - or maybe more accurately rationalize - the ongoing astronomical expense: our opponents in the Cold War scared the bejabbers out of us (and this applies to both sides). However, we aren’t there yet with the level of concern at the leadership level, let alone the general populace whose votes are purchased by programs, benefits and earmarked goodies. Look at the close of every major conflict the US has had in the 20th century. Right afterward, there was a major downsizing and de-emphasis on military capability - everyone looking for that peace dividend. Then the next conflict blows up and we are building the machinery (including tactics, techniques and procedures) for it from scratch.

Thus the atomic program, while perhaps an apt analogy, is a unique occurrence that transcended decades and many conflicts of all scales. And, virtually none of it was ever used! Sure, nuclear bombers were pressed into conventional missions, nuclear subs launch conventional arms on cruise missiles, but nothing at a scale that justified the expense of building and maintaining them for their primary mission - nuclear attack. All of it was a huge bluff - the game of deterrence, never intended to actually be used.

I don’t think we could get that kind of committment again out our leaders or our people, not one that lasts for sixty years, not for something that might never get used. The scale of vaccine production capability needed for staving off panflu is like the atomic program in that respect, except that the bug doesn’t respect the concept of deterrence - it just is and will do what it will do, irrespective of our threats.

Therefore, in order to maintain some vestige of an effective industrial base for vaccine production, there has to be a way to make it economically rational in some respect. Else, we have to get the general populace at least as aroused about the disease threat as they were about the Red Menace (or Capitalist Menace for those of you east of the Volga!)

Tom DVM – at 17:47

annon 22. I agree with you but that is the only way it will get done. There is no other option that I know of.

The problem for authorities is that the risk projections are still too fuzzy for them. I think they will sit on their hands until they suddenly realize that their asses are on the line (direct risk to their families) same as ours…but by then, as you have said, it will be too late.

If there ever was a certainty in public health, H5N1 is it…and if they can’t see it, they deserve to be ******* when it happens.

clark – at 18:49

I think that the “war footing” analagy is solid. WW1 killed 15,000,000 civilians and soldiers. 1918 flu killed 50,000,000- 100,000,000 soldiers and civilians. WW2 killed about 50,000,000 civilians annd soldiers.

A high CFR pandemic is going to destroy or very severely prune every business on Earth. If people are dead, sick, tramatized and out of work from flu- who are the drug companies going to sell their potions too? The chronically ill will be amongst the first to get sick. Who would buy Viagra or Xenical??

If big pharma thought about it deeply for, say 30 seconds, they would realize that an unopposed flu pandemic would wipe them off of the map. No business sector is in such a pivitol position to PROSPER from a pandemic (be heros, make money, be loved)- or to FAIL UTTERLY (no business, customers dead or too poor to buy anything, universilly hated and shunned by society- blamed for the deaths of millions etc)

It is really a no-brainer. They make the vaccines, they make money, they are heroes- Society is preserved

Tom DVM – at 18:52

Clark You make a great point. Maybe we should be selling this like Globablization in reverse…an economic necessity rather than a health necessity…maybe then the ***-***** would listen.

Tom DVM – at 18:54

Sorry, missed one *in the first part of the word. I use *** because I’m afraid Dem and Melanie would kick me off flu wiki if I used the real ones.

To get the answer check the flu wiki short page forms……./;-)

Leo7 – at 18:54

Tom:

I wonder if the November elections are a means to accomplish our goal. Like if we all start whispering, no massive push for vaccine, no voting. Why would I go out in a crowd to vote in flu season? Take about wasting a ton of money!

Tom DVM – at 18:55

Sorry, actually wrong again. I didn’t need that other *.

anon_22 – at 20:01

Tom, that’s one really confusing post. LOL

anon_22 – at 20:03

I’ve just put up a few posts on the MF59 thread on conflicts of interest.

14 June 2006

clark – at 08:34

Christian on CE found this

http://www.eurekalert.org/pub_releases/2006-06/idso-evp061306.php

Experimental vaccine protects lab animals against several strains of H5N1

Public release date: 13-Jun-2006 Contact: Steve Baragona sbaragona@idsociety.org 703–299–0412 Infectious Diseases Society of America

Nations are preparing to stockpile vaccines against H5N1, the strain of influenza virus that experts fear could cause the next flu pandemic. But will these vaccines remain effective as the virus mutates? Researchers present good news in the July 15 issue of The Journal of Infectious Diseases, now available online. Elena Govorkova, MD, PhD, Robert G. Webster, PhD, and coworkers at St. Jude Children’s Research Hospital in Memphis, Tenn., used reverse genetics to develop an influenza virus with two key proteins on its surface derived from an H5N1 strain. They inactivated the virus and used it to vaccinate ferrets. The vaccine protected the ferrets from getting sick when exposed not only to the flu strain from which the vaccine was made, but also two other strains, including a deadly strain labeled A/Vietnam/1203/04.

Cross-strain protection is exactly what one would need, as it would protect against newly emerging variants until a strain-specific vaccine can be developed. The reverse genetics method used by the St. Jude investigators would allow rapid vaccine preparation, which is crucial in a potentially fast-moving pandemic. Other undertaken vaccine approaches have serious shortcomings. Wild-type H5N1 vaccines, for example, cannot be produced on a large scale because of their marked virulence, and vaccines based on less-virulent H5N1 strains have so far been relatively poor stimulators of immunity in human trials.

In the study, the ferrets were vaccinated intramuscularly with one or two doses of vaccine. Both schedules induced a protective antibody response, but the two-dose schedule induced higher levels of antibodies that were cross-reactive to various H5N1 viruses. Human clinical trials have seen similar results, suggesting that two doses of vaccine will be required to effectively protect against an H5N1 flu strain.

In an accompanying editorial, Alan W. Hampson, MSc, of the Australian Influenza Specialist Group, noted that the successful use of a genetically modified whole-virus vaccine that produced protective antibodies against H5N1 virus in ferrets suggests that the ferret model has the potential to provide useful information in assessing vaccines when human data alone are inadequate.

“Possibly the greatest significance of the current study, he added, “is the demonstration of a significant cross-strain protective effect,” a finding that “strengthens the argument for stockpiling vaccines prepared from currently available H5N1 vaccine strains.”

15 June 2006

clark – at 06:23

bump

17 June 2006

MaMaat 01:18

bump

Hurricane Alley RN – at 02:15

bump

Hurricane Alley RN – at 02:39

bump

clark – at 03:16

bumpidy bumpidy bump bump bump!!

18 June 2006

Closed and Continued - BroncoBillat 01:32

Closed due to length. Conversation is continued here.

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