AFD - Vaccines - Studies and Developments

[sharon sanders]

NEJM : Baxter's Cell Cultured Vaccine




# 2063



http://afludiary.blogspot.com/



It is generally agreed that having an effective vaccine, in quantity, is the best way to combat an influenza pandemic. Even though vaccines don't confer 100% immunity, if enough of the population has immunity, it can effectively starve a virus of susceptible hosts and hopefully the pandemic will fade away.

Pandemic vaccines are problematic, however.

First, a targeted vaccine cannot be produced until a pandemic strain is identified, and using our current egg-based technology, it can take another 20-28 weeks to produce the first batches of vaccine.

Second, our global capacity for creating vaccines using this egg-based technology is limited. No one knows exactly how much we could produce in a year, but estimates are that only enough vaccine could be produced to inoculate 10%-15% of the world's population.

There are other problems, of course. Distribution of vaccines, particularly during a pandemic, could be very difficult. Having a vaccine at the manufacturing facility is only half the battle.
​

But the big bottleneck has been our egg-based manufacturing technology, and the holy grail of vaccine manufacturers has been the development of a cell-culture vaccine.


Yesterday the NEJM (New England Journal of Medicine) published two articles on Baxter International's cell-cultured vaccine, sparking an avalanche of media coverage.

The primary study may be read here.


A Clinical Trial of a Whole-Virus H5N1 Vaccine Derived from Cell Culture

Hartmut J. Ehrlich, M.D., Markus M?ller, M.D., Helen M.L. Oh, M.D., Paul A. Tambyah, M.B., B.S., Christian Joukhadar, M.D., Emanuele Montomoli, Ph.D., Dale Fisher, F.R.A.C.P., Greg Berezuk, M.S., Sandor Fritsch, Ph.D., Alexandra L?w-Baselli, Ph.D., Nina Vartian, Ph.D., Roman Bobrovsky, Ph.D., Borislava G. Pavlova, Ph.D., Eva Maria P?llabauer, M.D., Otfried Kistner, Ph.D., P. Noel Barrett, Ph.D., for the Baxter H5N1 Pandemic Influenza Vaccine Clinical Study Team




Here is how Reuters covered the story.

Monkey cells used for bird flu vaccine



June 12, 2008

WASHINGTON: A bird flu vaccine made from monkey cells instead of chicken eggs has been reported effective by corporate researchers.

The researchers, from drug company Baxter International, documented the use of monkey cells as a safe alternative for influenza vaccinations.


?Cell culture technology could represent the future of influenza vaccine production,? said virologist John Oxford of The Queen Mary School of Medicine in London.


Scientists had previously been using chicken eggs but they found it difficult to obtain the right type and observed that the virus, H5N1, kills chickens rapidly.


The trial, carried out on more than 250 people and reported in the New England Journal of Medicine, showed the vaccine produced a strong immune response in people who received two doses.
(cont.)
​

Admittedly, this sounds promising. But it is a little soon to start popping Champaign corks.


In a perspective article appearing in this month's NEJM entitled Vaccine Preparedness ? Are We Ready for the Next Influenza Pandemic? by Peter F. Wright, M.D., we are cautioned that while cell-culture technology may one day greatly increase our ability to produce vaccines, that we aren't there yet.

Dr Wright writes:

Are we prepared for pandemic influenza? We are not ready to put a vaccine in the field should H5 gain person-to-person transmissibilityor should another strain emerge. The work on novel vaccine approaches,however, suggests that we may still make it, if influenza continuesto stay in its lair and largely confine itself to avian hosts.
​

The conversion from egg-based manufacturing to cell-culture manufacturing will require expensive conversions of vaccine plants and will take time. We are still years away from seeing this new technology in widespread use.


Experts have cautioned that Baxter International used a different, and lower, standard for determining whether a vaccine conferred immunity than is normally used in the industry (see Helen Branswell's excellent coverage). This may have artificially raised the response rate, although Dr. Hartmut Ehrlich, lead author on the study, expressed confidence in this benchmark.


The Baxter vaccine also uses a whole unmodified virus (killed in the manufacturing process), instead of a split virus. While this is believed to produce a more robust immune response, it can also result in more adverse reactions.


The most common reactions reported among the 275 people in the Baxter study were injection site swelling and soreness and headache.


Another drawback is that the whole virus must be grown in a biosafety level III laboratory. Normally, we use a `split' virus, containing only part of the genetic material of a virus, rendering it `safer' to handle.


Dr. Wright in his perspective article points out that we've used whole, live polioviruses for many years to produce inactivated polio vaccine, and have done so without incident. Still, proper biocontainment at the manufacturing site will be an issue.


The bottom line is: This is a step forward, perhaps even a big step.

But it will probably take years, and a substantial financial commitment by the world's vaccine manufacturers to translate this research into a global capacity to rapidly produce large quantities of cell-cultured vaccine.

posted by FLA_MEDIC @ 6:39 AM

 

[HenryN]

Re: AFD - Vaccines - NEJM: Baxter's Cell Cultured Vaccine

Re: AFD - Vaccines - NEJM: Baxter's Cell Cultured Vaccine

NEJM : Baxter's Cell Cultured Vaccine






Experts have cautioned that Baxter International used a different, and lower, standard for determining whether a vaccine conferred immunity than is normally used in the industry (see Helen Branswell's excellent coverage). This may have artificially raised the response rate, although Dr. Hartmut Ehrlich, lead author on the study, expressed confidence in this benchmark.



posted by FLA_MEDIC @ 6:39 AM

The response rate can be defined using any end point. The industry standard is a titer of 40. Baxter used a titer of 20, because the number of patients who generated a titer of 40 more more was quite low and would even raise eyebrows of popular press reporters.

The titer is what the titer is and anyone can state hopes and dreams for either number, but neither number has been directly tested (challenged) in humans, due to ethical considerations.

 

[sharon sanders]

Australian Vaccine Wins Approval



# 2076


On May 1st we got word that CSL's Panvax H5N1 vaccine had received preliminary approval from the Australian Drug Evaluation committee.

Today is has been announced that the vaccine has received final approval.

This report from Xinhua News.

Australia develops human vaccine for bird flu
www.chinaview.cn

2008-06-17 14:20:19


CANBERRA, June 17 (Xinhua) -- Australia has developed a human vaccine for bird flu, federal Health Minister Nicola Roxon announced here on Tuesday.

"The first ever Australian-made vaccine to protect humans from future bird flu pandemics has been granted approval for use in the event, of course, of an avian influenza outbreak," Roxon told reporters.

The vaccine, developed by CSL, would protect humans against the H5N1 strain of influenza responsible for outbreaks of bird flu in Asia, the Middle East, Europe and Africa, Roxon said.

"We know, of course, that if there is an outbreak that affects Australians, we need to make sure that we are properly prepared," she said.

"What we now have, courtesy of the work done by CSL ... is an Australian-made and able to be manufactured in Australia vaccine which will be able to respond to any new strain of a virus."

"We are very pleased that now that approvals have been granted that if we are in a situation which, of course, we hope we won't be, of a human-to-human virus taking hold in Australia, we will be able to quickly respond," she added.

She also said that in that event, there would be no need to go through the approval process, and the safety of the vaccine had been assessed for adults aged 18-64 and those aged over 65.

More than 160 million dollars (150 million U.S. dollars) had been provided in this year's federal budget to replenish Australia's vaccine stockpile.
​

posted by FLA_MEDIC @ 7:21 AM

 

[sharon sanders]

Re: AFD - Vaccines - Studies and Developments

WHO To Consider Larger Vaccine Stockpiles



# 2094



The take-away-message from the Kuala Lumpur Infectious Disease conference has obviously been that the world cannot let down its guard against a pandemic.


Dr. Julie Gerberding made that abundantly clear yesterday, and today we learn that the WHO will consider expanding the stockpile, and role, of pre-pandemic vaccines this fall.

This from Reuters.

Experts to mull if more flu pandemic drugs needed-WHO

Sun 22 Jun 2008, 10:30 GMT

By Tan Ee Lyn

KUALA LUMPUR, June 22 (Reuters) - Experts will discuss in November if the World Health Organisation needs to maintain a bigger arsenal of vaccines to help fight a flu pandemic, a top WHO official said on Sunday.

Scientists have warned for years about a flu pandemic that could be triggered by the H5N1 bird flu virus, which kills between 60 and 80 percent of the people it infects.

David Heymann, assistant director-general for communicable diseases at the WHO, said the current plan was for the WHO to maintain up to 100 million doses of what are known as "pre-pandemic' vaccines.

These would be used for essential populations in countries that need them, such as healthcare, police and security workers.

"They (a WHO-commissioned advisory committee of experts) will determine whether or not there should be a greater stockpile or even consider vaccinating populations against H5N1 as an insurance policy," Heymann told a news conference on the sidelines of an infectious disease conference in Kuala Lumpur.
(Cont.)

​

posted by FLA_MEDIC @ 9:40 AM

 

[sharon sanders]

Re: AFD - Vaccines - Studies and Developments

Branswell On Vaccine Strength Measurements




# 2095



Helen Branswell of the Canadian Press does again what she does best, providing us with a clear and concise explanation of a complicated subject; in this case the relative effectiveness of influenza vaccines.


Right now, each manufacturer is free to choose their own method and rationale for determining the strength, and efficacy, of their product. Without an agreed upon standard, this makes it very difficult to compare vaccines.


This is just a snippet. As always with stories by Ms. Branswell, it is well worth following the link to read the entire article.


A hat tip to Shiloh on Flutrackers for posting this story.

Bird flu vaccine strength could be under-or overestimated due to test variability
​

Published Sunday June 22nd, 2008 TORONTO - A study comparing the tests being used by vaccine manufacturers to gauge the effectiveness of their H5N1 avian flu vaccines shows there is a lot of variation in the sensitivity of the tests, the British scientist leading the effort says.

Differences in the sensitivity of the tests mean companies could be underestimating or overestimating the power of their vaccines as they try to work out what is the smallest protective dose, experts admit.

As things stand now, there is no way to usefully compare the results of one company's clinical trials for their vaccine with a competitor's findings.

"If Company A's assay (test) happens to be 10 times more sensitive than Company B's, Company A and Company B could be evaluating the exact same thing but reach different answers about whether they worked or not," says Dr. John Treanor, a vaccine expert who knows of the study but is not involved in the work.

The effort, which included trying to develop an international standard against which H5N1 antibody tests could be measured, is being led by Dr. John Wood, a prominent influenza virologist with Britain's National Institute for Biological Standards and Control.

"The purpose of this is not to assess one lab against another. It really is to develop a consensus on the values that are obtained," Wood explains.

"It allows WHO and governments and anyone, really, to make the comparisons."
(Cont.)
​

posted by FLA_MEDIC @ 12:37 PM

 

[gsgs]

Re: AFD - Vaccines - Studies and Developments

> estimates are that only enough vaccine could be produced
> to inoculate 10%-15% of the world's population.

source ? This could be an old estimate from times when only egg-based
vaccines were available.

As I see it, they could scale up production as long as it is being
paid for.
(which could be a problem for 3rd world, though)

 

[gsgs]

Re: AFD - Vaccines - Studies and Developments

translated from the German thread:
------------------------------------------------------------------------------- http://www.rki.de/nn_200126/DE/Conte...uenza/FAQ.html
Paul Ehrlich institute, spring 2006:
> After an outbreak of a pandemic according to present estimate
> of production possibilities in the unfavorable case it needs 22 weeks (= 5.5 months),
> until the first vaccine doses can be delivered
> In a most favorable case which is aimed for, the present
> Concept it takes 10 weeks (2.5 months), until the first vaccine doses are available.
> This is achieved by a ?seed virus ?with
> suitable virus components a shortening of the production on fewer phases:
> Job preparation: 10 weeks
> Production of 80 million doses for the first inoculation: 6 weeks
> Production of 80 million doses for the second inoculation: 6 weeks

http://www.pei.de/nn_157240/DE/infos...zulassung.html
> 9) the WHO is
> the work for the development and evaluation by which are applicable trunks;
> for the production of vaccines against the new influenza trunks during that
> Phase 0 readiness stage 1 or 2 begins. The time for the production of a suitable
> Trunk becomes between 1 week (if more pathogenic, antigen identical virus trunk to
> Order stands) and for 3 months (if reassortant viruses must be manufactured) .
> From reverse genetics manufactured virus trunks can be manufactured in approx. 3 weeks.
> Here however possibly 1-2 months are needed for the safety testing.

> 10) the manufacturers indicated that they would need 9-18 weeks, around those
> to be able to make available first seed virus quantities of the vaccine. The timeframe
> depends on the necessity, which virus trunk for growth in the different
> To adapt cell substrates. The guideline to dossier structure and - contents for
> the application for admission
> for a pandemischen influenza vaccine offers the possibility, which
> first step; to accelerate the production process (i.e. testing the seed loads).

so, in the important case of a severe pandemic with high vaccine priority
I assume it takes ~3 months until more than 50% of the population is vaccinated,
4-5 months for 100%

 

[gsgs]

Re: AFD - Vaccines - Studies and Developments

with the cell-based production technology, the time until
delivery of the vaccine shortens from 20-28 to 12 weeks.

[says Baxter]


source in German:
http://www.aerztezeitung.de/medizin/...pe/?sid=501422


-----edit1-------

but let's be careful, they often use tricky wording.
They won't probably deliver all the vaccine at once, so this could be the time
until the first doses are being delivered.
According to the PEI-website from 2006 (co cell-based technology available at that time)
it would take another 6 weeks to produce the full 80M doses.
It also takes an estimated 3 weeks to build up immunity, and for the Baxter-vaccine this
time may have to be redoubled according to the graphic above.

 

[sharon sanders]

Re: AFD - Vaccines - Studies and Developments

Expert: Poultry Vaccine Losing Effectiveness



# 2124



While the use of poultry vaccines is controversial, and certainly not universally accepted, in many countries where the H5N1 bird flu virus is endemic their use is widespread.


The concern has always been that vaccinated flocks could contribute to the silent spread of the disease due to incomplete protection from the virus, resulting in asymptomatic, but infectious birds.


In 2006, Vietnam's vaccination program was hailed as having brought containment and control to that bird flu ravaged nation. Despite its critics, it seemed that vaccination programs were effective.


Over the past year, however, we've seen more reports of asymptomatic, but infected, birds. In some cases, in previously vaccinated flocks.


Now we are getting this warning, from Professor Yuen Kwok-yung of Hong Kong, that the H5N2 poultry vaccine being used to protect birds is losing its effectiveness.


This story from Monsters & Critics. Follow the link to read the whole thing.

Hong Kong expert warns flu vaccine for chickens losing efficacy


Jul 8, 2008, 4:19 GMT

Hong Kong - A vaccine used to stop outbreaks of the deadly bird flu virus in chickens in Hong Kong for the last seven years is losing its effectiveness, a leading microbiologist warned Tuesday.

Professor Yuen Kwok-yung said the vaccine, which protects chicken from the H5 strain of the virus, is becoming less effective and the city risks further outbreaks because total failure is inevitable.

The head of microbiology at the University of Hong Kong told the South China Morning Post the virus was mutating and shifting away from the Fujian strain of H5N2 that it was developed for.

His warning follows an outbreak of H5N1 virus in four wet markets in Hong Kong in June, the first in years in the former British colony.

Yuen, who is part of a team investigating the outbreak, said the city must get rid of all live chickens in markets before the vaccine becomes completely ineffective.

He said tests showed that in 2005 vaccine was producing only a quarter of the antibodies to protect against the virus compared to the level produced by the same vaccine in 2001.

He said some chickens showed an antibodies level at the 'alarm stage' which meant the protection was minimal.
(Cont.)

​

posted by FLA_MEDIC @ 7:51 AM

 

[sharon sanders]

Re: AFD - Vaccines - Studies and Developments

Prepandemic Vaccine Strategies



# 2153



Over the past few years the world has produced a few dozen million doses of various pre-pandemic H5N1 vaccines. A handful of countries have small stockpiles, and a few, like Switzerland, reportedly have enough to inoculate their entire nation.


As these vaccines are all based on older clades of the H5N1 bird flu virus, how effective they would be against a mutated strain is largely unknown.

The problem is that these vaccines have a limited shelf life - normally somewhere between 18 months and 2 years. Over the next year it is likely that millions of doses will expire.


With the prospect of `using them, or losing them' looming large, the idea of early administration of them to essential workers is now under consideration. Japan is one country currently considering that option.


Influenza vaccines generally produce the highest immune responses during the first 5 or 6 months after administration, then gradually lose their effectiveness. The concern is that giving the vaccine too early would result in greatly reduced protection if and when a pandemic were to erupt.


New research, published in the August edition of The Journal of Infectious Diseases , appears to bolster hopes that early administration of a prepandemic vaccine can prime the recipient for a later vaccine.


Subjects who received an early, experimental vaccine, eight years ago in Hong Kong were given a single booster shot of a clade 1 H5N1 vaccine.


Normally it takes two shots over a 30 day time span to achieve an acceptable immune response. In this case, a single `booster shot' produced an encouraging 64% immune response.



Exactly how effective this strategy would be under real pandemic conditions is unknown, but it does lend support to the idea that soon-to-expire vaccines could be `stored in people', instead of being disposed of when they reach the end of their shelf life.


These snippets come from a press release by the Infectious Disease Society of America.

Booster vaccination may help with possible future avian influenza pandemic


New evidence suggests that a booster vaccination against H5N1 avian influenza given years after initial vaccination with a different strain may prove useful in controlling a potential future pandemic. The study is published in the August 1 issue of The Journal of Infectious Diseases, now available online.

<snip>

The study, conducted by Nega Ali Goji, MD, and colleagues from New York, Maryland, and Alabama, gave a single booster dose of a vaccine based on a clade 1 H5N1 virus circulating in Vietnam in 2004 to subjects who eight years earlier had received two doses of a vaccine based on the original, clade 0 virus that appeared in Hong Kong in 1997. Sixty-four percent had a positive immune response, which compares favorably to the results of a previous study using two doses of the clade 1 Vietnam virus, in which only 43 percent of those vaccinated had a positive immune response.


The results not only support the booster technique, but also show that even though the virus had mutated since the initial vaccination, using it to boost an earlier vaccine is more effective than simply vaccinating subjects with the most current vaccine. These findings are important given the fact that influenza viruses are mutating constantly.

<snip>

In an accompanying editorial, Gregory A. Poland, MD, of the Mayo Clinic College of Medicine, noted that some are already looking to begin such prevaccination primers against H5N1 influenza. For example, Japan is planning to immunize health care workers starting in 2009, and the U.S. Department of Defense is offering a vaccine to those in high risk specialties.

Dr. Poland pointed out that new studies are needed to investigate different types of vaccine administration, deal with vaccinations that prevent death but not infection and illness, search for more broadly cross-protective influenza vaccines, and collect data on the vaccination of those who are not healthy adults.

Although, he said, "determining who should receive these vaccines, when, and in what order and under what circumstances deserves widespread debate," he agrees that the findings of the study are novel, as they "suggest that such a prime-boost strategy using vaccines derived from different H5 clades, separated by years, may be worthwhile, immunologically feasible, and safe."
​

posted by FLA_MEDIC @ 9:13 AM

 

[gsgs]

Re: AFD - Vaccines - Studies and Developments

> Influenza vaccines generally produce the highest immune responses
> during the first 5 or 6 months after administration, then gradually
> lose their effectiveness

I think the height is ~3weeks after administration and then gradually declines.
It had been suggested to give 2 doses per season in some
settings because of this

 

[sharon sanders]

Re: AFD - Vaccines - Studies and Developments

UK Study: Benefits Of Vaccinating Children Against Influenza






# 2203


Children are often a prime vector for respiratory illnesses.

One need only look in at any daycare facility or school to see a wide range of sniffles, snuffles, and coughs. And of course, children readily spread these viruses amongst themselves, and to adults as well.

If one kid in school gets a cold, or the `flu', you can bet that a lot of others won't be far behind.

The proposal has been made that, by routinely vaccinating children against influenza, the amount of flu circulating in a community can be drastically reduced.

Here is an article from the London Telegraph, detailing this proposal. Follow the link for the full article.

Vaccinating all children under 16 could cut flu cases 'by up to 97 per cent'


Flu could be virtually wiped out if all under 16s were vaccinated against the disease, a new report suggests.



By Kate Devlin, Medical Correspondent
Last Updated: 4:00PM BST 04 Aug 2008

Giving every baby and schoolchild in England and Wales the jab could reduce cases of the main strains of the disease by up to 97 per cent, the Health Protection Agency (HPA) estimates.

Ensuring that all babies between the ages of six months and two years received a flu shot could cut the number of cases by between one tenth and a fifth, according to the analysis.

The HPA estimates are based on preventing the two main strains of the virus, known as Influenza A and Influenza B, thought to be responsible for nine out of 10 flu cases in Britain.

However, the agency said that it was not yet advocating the widespread use of the vaccine in young people and described the results as "preliminary".

Experts estimate that influenza contributes to the death of more than 12,000 people in Britain every year and around 15 million Britons are given an annual flu jab in an attempt to prevent the disease and the complications it can cause.

Currently the elderly and those most at risk, such as asthma sufferers or those with heart disease, receive the jab while a number of companies also offer workplace-based vaccination programmes.

However, many adults are thought to initially contract the illness from children.

(Continue . . .)
​

Of course, all of this is theoretical at this point.

And there would be likely be resistance by many parents. Childhood vaccinations are generally very safe, but there have been rare instances where children were harmed by vaccines.


There are many who subscribe to the idea that autism is caused by the addition of thimerosal, which contains 50% mercury, as a preservative in vaccines. While no causal link has ever been established, the fear persists in many parents.


So far, the UK's Joint Committee on Vaccination and Immunisation (JCVI) has not endorsed the idea of vaccinating all children.

For now, this remains a proposal.

Albeit an interesting one.


posted by FLA_MEDIC @ 12:56 PM

 

[sharon sanders]

Re: AFD - Vaccines - Studies and Developments

Vietnam Reporting Progress On Human Vaccine Trials


# 2249



Like many countries, Vietnam has been working towards developing their own version of a human H5N1 vaccine. During a pandemic, obviously, the more countries able to produce a vaccine the better.

Previous blog entries on their progress can be found here, here, and here.

Vietnam may produce bird flu vaccines for humans late next year
www.chinaview.cn

2008-08-22 13:45:31

HANOI, Aug. 22 (Xinhua) -- Vietnam plans to make vaccines against bird flu virus strain H5N1 for humans in late 2009 after successful trials, according to local newspaper Pioneer on Friday.

A dose of the vaccine, developed by a local company named Vabiotech under Vietnam's National Hygiene and Epidemiology Institute, will have a selling price of some 30,000 Vietnamese dong (1.8 U.S. dollars).

The vaccine, called Fluvax, has been tested on local volunteers, and then proved effective. The health of the volunteers is good.

Vietnam has confirmed a total of 106 human cases of bird flu infections, including 52 fatalities, in 36 cities and provinces since bird flu started to hit the country in December 2003.

Since late 2003, the disease has killed and led to the forced culling of dozens of millions of poultry in Vietnam.
​

Posted by FLA_MEDIC at <a class="timestamp-link" href="http://afludiary.blogspot.com/2008/08/vietnam-reporting-progress-on-human.html" rel="bookmark" title="permanent link"><abbr class="published" title="2008-08-22T08:09:00-04:00">8:09 AM</abbr>

 

[sharon sanders]

Re: AFD - Vaccines - Studies and Developments

DNA Vaccine Shows Promise In Mice



# 2271



The good news appears to be, if you are a mouse and we have a pandemic, there are a lot of treatment options open to you.


If you are a human . . . well, you'd still better hope that a pandemic holds off for a few more years.


Promising or not, most of the experimental treatments and vaccines we are reading about today won't be ready for prime-time (read: human use) for several years at least.


And some may never translate into a practical treatment for humans.


None of this is to diminish the value of the research being done. I find the details fascinating, and am hopeful that one day some of these discoveries will provide us with new tools to fight, and perhaps even prevent, another pandemic.


We're just not there yet.


This report from Reuters.

Bird flu vaccine gives strong protection in mice

Mon Sep 1, 2008 10:18pm BST

HONG KONG (Reuters) - An experimental bird flu vaccine that uses DNA from various strains of the H5N1 virus appears to trigger a strong immune response in mice after it is injected straight into the muscles, a study has shown.

In the journal Cell Research, scientists in Taiwan and the United States said the vaccine protected mice fully against H5N1 strains from Vietnam, Turkey and China's eastern Anhui province.

"We injected it into mice and after more than a week, the mice were immunized and we challenged the mice with live virus strains from Vietnam, Indonesia, Turkey and Anhui," Chi-Huey Wong from The Genomics Research Center in Taiwan's Academia Sinica told Reuters by telephone.

"The mice were fully protected from the strains from Vietnam, Turkey and Anhui, while 80 percent (of mice) were protected from the Indonesian strain, but that's still very high."

Another group of mice which were not immunized all died within days of being infected with lethal doses of the virus.

Vaccines using DNA are a departure from the traditional way vaccines are made -- painstakingly grown in chicken eggs, which could well be in very short supply in the case of a pandemic.

The H5N1 avian influenza virus currently mostly affects birds and is endemic in flocks in many parts of Asia. It has also swept through flocks in Africa and occasionally in Europe.

(Continue)
​

Posted by FLA_MEDIC at <a class="timestamp-link" href="http://afludiary.blogspot.com/2008/09/dna-vaccine-shows-promise-in-mice.html" rel="bookmark" title="permanent link"><abbr class="published" title="2008-09-02T10:32:00-04:00">10:32 AM</abbr>

 

[gsgs]

Re: AFD - Vaccines - Studies and Developments

is anyone in the meantime addressing the decisive question,
how much vaccine production could be scaled up in a pandemic ?

(with additional money, with relaxed security requirements)


this is one of the strangest things in the panflu-discussion,
why/how this most important subject is being avoided
by flubies as well as journalists as well as vaccine producers
as well as officials

 

[sharon sanders]

Re: AFD - Vaccines - Studies and Developments

Sunday, September 07, 2008

Filling In The Rest Of The Story



# 2283




Below is a story that has been widely carried by many news outlets over the past couple of days. This version came from the Belfast Telegraph, but almost all of the write-ups are the same.


Scientists are beginning clinical trials on a new, universal flu vaccine. (And yes, this is both exciting, and important news.)


But read the article below, then we'll discuss it.

Trials begin on a vaccine that may beat flu ? and bird flu


Saturday, 6 September 2008

Clinical trials of a new universal flu vaccine that could offer long-term protection against strains including human mutations of bird flu are starting at Oxford University.


If successful, the jab would overcome two problems ? at the moment, doctors can only vaccinate against certain strains of flu and have to change the formulation every year in response to the developments of new variants.


Lead researcher Dr Sarah Gilbert, of the university's Jenner Institute, said: "This approach to influenza vaccination is unsatisfactory for use against seasonal influenza and of little use when new types of flu begin to infect humans from birds.


"It leaves manufacturers with a few months to produce the necessary stocks, the vaccine has to be administered to at-risk populations within a short time window, and those receiving the injection will all have to be vaccinated again the following year."


If initial trials on 12 volunteers are successful, the vaccine will have further testing before it can be approved for use.


Existing flu vaccines work by producing antibodies in reaction to proteins on the surface of the virus.


But it is those proteins that change between strains and develop over time, so the new vaccine instead attacks internal proteins that remain unchanged. This should make it universally effective

​

It all sounds very encouraging, doesn't it? If successful, we could defeat influenza . . . even bird flu!


Of course, we are cautioned, `further testing' will be required if this first human trial goes well.


How much further testing?



Well, to find that answer we have to go to the BBC's story of two days ago, one which is considerably longer, and more detailed than the one reprinted widely around the world yesterday and today.


In that version, well written by Emma Wilkinson and with a rather sedate headline of Universal flu vaccine tests start, early on we are told that:

Experts said such a vaccine was the "holy grail" for flu researchers but there was still a long way to go.
​

And a bit later in the article, we are informed by the lead researcher, Dr. Sarah Gilbert that:

But she added the research team had five to 10 years of further tests ahead of them.
​

And lastly,

Professor John Oxford at Queen Mary, University of London said such a vaccine would be the "ultimate prize".

"But it's a fairly difficult prize to get - it may just be a question of luck.
​

Hmmm, not quite as upbeat.



But we can fix that.


Saying `the vaccine will have further testing before it can be approved for use' sounds so much better than there being five to 10 years of further tests ahead of them.



Both statements are technically correct, after all.


And the cautionary statements by other experts? Just omit those. No point cluttering up a good story with that sort of thing.


What we have left is a story suitable for the masses. One that avoids introducing conflicting ideas that only serve to confuse the reader. One devoid of hard to absorb numbers, like 5 and 10.


And it's a shorter story that fits better in-between advertisements.


Always a plus.


Admittedly, I'd be a bit more ecstatic about this research if I hadn't read the BBC version; the one burdened with all those pesky facts and opinions.


Luckily, given the quality of the coverage I've seen on this story, most people won't have that problem.

Posted by FLA_MEDIC at <a class="timestamp-link" href="http://afludiary.blogspot.com/2008/09/filling-in-rest-of-story.html" rel="bookmark" title="permanent link"><abbr class="published" title="2008-09-07T09:46:00-04:00">9:46 AM</abbr>

 

[sharon sanders]

Re: AFD - Vaccines - Studies and Developments

Lancet: An Argument For Stockpiling Pre-Pandemic Vaccines


# 2319




Pre-pandemic vaccines - in this case, vaccines based on an existing strain of the H5N1 virus - are hoped will provide at least some protection, even against a mutated avian flu virus.

How much protection is an open question.


Perhaps not enough to prevent infection (although that would be nice), but hopefully enough to moderate the effects of the illness and reduce the mortality rate.

If nothing else, it is hoped that such vaccinations might `prime' a recipient's immune system to allow them to need only one booster shot during a pandemic.
​

Japan, which currently has about 20 million doses of a soon-to-expire pre-pandemic vaccine, is contemplating inoculating millions of their healthcare and critical infrastructure employees early next year.



Switzerland has reportedly purchased 8 million doses of pre-pandemic vaccine, enough to inoculate their entire citizenry should they choose. Denmark, it was widely reported in January of 2007, ordered in enough pre-pandemic vaccine for half of their population. And in Australia, there has been talk of inoculating their entire nation.



New Zealand has announced they had enough pre-pandemic vaccine on hand for 100,000 essential workers, and the UK is exploring the purchase of large quantities of vaccine.


The United States reportedly has enough pre-pandemic vaccines, based on several earlier clades of the H5N1 virus, to inoculate about 20 million essential workers.


While the WHO (World Health Organization) has stopped short of recommending that countries stockpile a pre-pandemic vaccine obviously not all nations agree.


Pulling the trigger, however - actually distributing this vaccine before a pandemic erupts - is not an easy decision. There are always worries that there could be a small number of serious side effects when millions of shots are given.


Acceptable in the face of a deadly pandemic, but less so when this is a prophylactic move for a pandemic that hasn't started.



Today, we get a detailed opinion piece in the The Lancet Infectious Diseases journal, supporting the idea of early pre-pandemic vaccinations, particularly among high risk populations.



As the author's point out, once a pandemic begins it will become more difficult to deliver a pre-pandemic vaccine to the population. They go so far as to suggest :

The maximum benefit from using a prepandemic vaccine may be gained from priming populations before phase 4, when systematic supply, distribution, and vaccination strategies can be put in place.
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There is a good deal of information presented here, and it is well worth reading it in its entirety.


The abstract may be freely read, but registration (it's free) is required to read the entire journal article.


I've reproduced the abstract below (reparagraphed for readability).

The Lancet Infectious Diseases 2008; 8:650-658
DOI:10.1016/S1473-3099(08)70232-9
Personal View

Stockpiling prepandemic influenza vaccines: a new cornerstone of pandemic preparedness plans

Dr Lance C Jennings PhD , Prof Arnold S Monto MD , Prof Paul KS Chan MD , Prof Thomas D Szucs MD and Prof Karl G Nicholson MD

Summary

The history of pandemic influenza, along with the evolving epizootic of the highly pathogenic avian influenza A (H5N1) virus and the severity of associated human infections, serve as a warning to the world of the threat of another influenza pandemic.

Conservative estimates suggest that up to 350 million people could die and many more would be affected, causing disruption to health-care systems, society, and the world's economy.

WHO has encouraged countries to prepare in advance by developing influenza pandemic preparedness plans that involve public-health and pharmaceutical interventions.

Vaccination is a cornerstone of these plans; however, a pandemic vaccine cannot be manufactured in advance because the next pandemic virus cannot be predicted.

The concepts of vaccine stockpiling and prepandemic vaccination have thus become attractive. Human H5N1 vaccines are currently available and can induce heterotypic immunity.

WHO and governments should give urgent consideration to the use of these vaccines for the priming of individuals or communities who would be at greatest risk of infection if an H5N1 influenza pandemic were to emerge.
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[sharon sanders]

Re: AFD - Vaccines - Studies and Developments

CBO: Refocusing Our Vaccine Efforts



# 2321



From CIDRAP (Center for Infectious Disease Research & Policy) News we get an excellent summary of the CBO's (Congressional Budget Office) recent report entitled U.S. Policy Regarding Pandemic-Influenza Vaccines (PDF file).


Essentially the CBO is recommending that more research be put towards developing and approving adjuvants - additives to vaccines that enhance the body's immune response - in order to lower the amount of antigen required to make an effective vaccine.


If successful, this would go a long way towards helping us meet the goal of being able to produce enough pandemic vaccine for the entire nation within six months of a pandemic outbreak.

As always, I've just reproduced a snippet of this CIDRAP article. It is well worth reading in its entirety.

Report suggests refocusing US pandemic vaccine efforts


Lisa Schnirring and Robert Roos

Staff Writers
Sep 22, 2008 (CIDRAP News) ? The Congressional Budget Office (CBO) suggests in a new report that an increased focus on the development of vaccine adjuvants could save the US government money while improving the nation's preparedness for an influenza pandemic.


Noting that the government has been spending large amounts to increase egg-based flu vaccine production capacity and develop cell-based production capacity, the CBO says it might be wise to shift some funds into the development of adjuvants (chemicals that reduce the amount of vaccine needed to generate an immune response).


"The arithmetic of pandemic vaccination changes dramatically . . . if adjuvanted vaccines are developed and approved," says the report. If adjuvants fulfill their promise, it adds, the egg-based and cell-based production facilities now available or under construction would be enough to meet HHS's goal of vaccinating every US resident within 6 months of the start of a pandemic.


The CBO published its findings on Sep 15. The 52-page report gauges progress the Department of Health and Human Services (HHS) has made since 2005, when it outlined two main vaccine goals in its pandemic plan: to increase production capacity by 2011 to vaccinate the entire US population within 6 months of a pandemic onset and to stockpile enough vaccine to inoculate 20 million people shortly after a pandemic begins.

(Continue reading . . . )
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The Congressional Budget Office's Director has a blog summary as well, which may be viewed here.






But adjuvants are not without controversy, as Maryn Mckenna explained in Part 4 (The promise and problems of adjuvants) of her award winning series The Pandemic Vaccine Puzzle.

While adjuvants hold the greatest promise for dose-sparing, they also provoke trepidation because they are by definition immune-system activators.While many have been tested over the years, few have entered the market, because they proved too reactogenic to be acceptable to consumers or safe.

Only one set of adjuvants, aluminum salts or alum (aluminum hydroxide, aluminum phosphate, and potassium aluminum sulfate), is licensed in the United States. Aluminum adjuvants and MF59, an oil-in-water emulsion that contains squalene (an oil found in some fish oils), are licensed in Europe (see Bibliography: Petrovsky 2007).
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Mayrn McKenna, author of Beating Back The Devil, and editor of the Superbug (MRSA) blog, is one of the most respected science writers in the the business.

For a full overview of the pandemic vaccine issue, I can think of no better resource than Maryn's 7 part series.

Part 1: Flu research: a legacy of neglect
Part 2: Vaccine production capacity falls far shortPart 3: H5N1 poses major immunologic challengesPart 4: The promise and problems of adjuvantsPart 5: What role for prepandemic vaccination?Part 6: Looking to novel vaccine technologiesPart 7: Time for a vaccine 'Manhattan Project'?Bibliography
​

 

[sharon sanders]

Re: AFD - Vaccines - Studies and Developments

Study: The First Wave Of the 1918 Pandemic May Have Acted As A Vaccine



# 2352


With somewhere around 50 million deaths worldwide, and 675,000 fatalities just in the United States, the Spanish Flu of 1918-1919 is hard to describe as anything but horrific.

But evidence is emerging that it could have been worse.

That during the Spring of 1918, a milder version of the virus affected millions of people, killing very few of them. Of those infected, the vast majority picked up immunity against the killer flu that was to come in the fall.

Had a mild wave not come first, millions more would likely have died in the fall of 1918.


Robert Roos of CIDRAP gives us a detailed look at this study, along with comments from a variety of researchers and epidemiologists including Dr. Michael Osterholm.


I've just printed the opening paragraphs to what is a lengthy, but important article. It is well worth your time to follow the link to read the entire article.





Study: First flu wave in 1918 was vaccine for some

Robert Roos

News Editor

Oct 2, 2008 (CIDRAP News) ? In the influenza pandemic of 1918, those who got sick in the first wave of illness were up to 94% less likely to fall ill when the second and much more severe wave struck, according to a new analysis of historical data.

The authors, led by historian John M. Barry, sifted data mostly from US Army camps, along with some from the British navy and British cities, to conclude that infection in the first wave acted like a vaccine, conferring immunity that protected people when the second wave arrived. Barry wrote the 2004 book The Great Influenza, a chronicle of the pandemic.

Their analysis "strongly points to cross-protection between outbreaks of respiratory illness during spring and early summer of 1918 and the influenza pandemic wave in the fall of 1918. The cross-protection effect was estimated to range from 35% to 94% for clinical illness and from 56% to 89% for mortality," says the report, published online by the Journal of Infectious Diseases.

The authors say their findings suggest that when novel flu viruses emerge and initially cause a mild wave of illness, public health authorities should think twice before taking aggressive steps to limit exposure, since people infected with the virus might benefit later on if the virus grows more virulent and triggers another wave of cases.

Besides Barry, the authors are Cecile Viboud of the Fogarty International Center in Bethesda, Md., and Lone Simonsen of George Washington University in Washington, DC.

<snip>

Barry JM, Viboud C, Simonsen L. Cross-protection between successive waves of the 1918-1919 influenza pandemic: epidemiological evidence from US Army camps and from Britain. J Infect Dis 2008 Nov 15;198 (early online publication) [Abstract]


(Continue)

 

[sharon sanders]

Re: AFD - Vaccines - Studies and Developments

October 5, 2008

Vaccine Plant Cancellation In US


# 2361


Maryn McKenna, a contributing writer for CIDRAP (Center For Infectious Disease Research & Policy) News, has a detailed and disturbing story about the collapse of a plan to have Solvay Pharmaceuticals build a vaccine manufacturing plant in the Southeastern United States.

Solvay Pharmaceuticals was one of 5 firms that shared in $1 Billion dollars in grants from the U.S. government in 2006, to help them develop new vaccine technologies.
​

With comparatively little vaccine production actually done on our shores, the United States fears it is particularly vulnerable to vaccine shortages during a pandemic.


The goal of the HHS has been to encourage domestic vaccine production and to fund research into newer, and faster, vaccine production technologies.


As Maryn shows us, this isn't as easily accomplished as one might hope.


This is just the opening few paragraphs, by all means follow the link to read the entire article.

Plant cancellation shows problems in flu vaccine business


Maryn McKenna

Contributing Writer

Oct 3, 2008 (CIDRAP News) ? A flu vaccine manufacturer's decision not to build a US facility has highlighted the perpetual mismatch between flu-shot supply and demand?and the reality that the mismatch may undermine plans for pandemic flu vaccines.

On Tuesday, Solvay Pharmaceuticals Inc. of Marietta, Ga., announced that it was canceling plans to build a US flu-vaccine manufacturing plant, a $386 million project that Birmingham, Ala., and Athens, Ga., have been competing for. The plant would have made both seasonal and pandemic flu vaccines?but at just about the moment when a final site selection was expected, the company announced that the economics of the two-year-old deal no longer make sense.

Solvay Pharmaceuticals is the US subsidiary of a Brussels-based conglomerate that makes plastics, industrial chemicals, and pharmaceuticals, including an egg-based flu vaccine called Influvac that is sold in Europe and Canada but not in the United States. Solvay also makes flu vaccine by cell culture, a newer technique that does not depend on chicken eggs; the vaccine is made in the Netherlands and has been approved for sale there, though the plant where it is made is still undergoing validation.

Establishing flu-vaccine manufacturing within the United States, especially cell-culture manufacturing, is a dearly sought goal of the federal government. Only one of the five manufacturers that sell into the US seasonal-flu market makes its vaccine within US borders. That has led to fears that, if a pandemic began, vaccines would not reach the US, because the countries where companies are based might hold back whatever is made there. The government has also been eager to develop domestic cell-culture manufacturing because it is not dependent on egg production, is not imperiled by viruses such as avian influenza H5N1 that are lethal to chickens and chicken eggs, and can be scaled up rapidly if necessary.

(Continue Reading . . .)

​

Maryn McKenna, author of Beating Back The Devil, and editor of the Superbug (MRSA) blog, is one of the most respected science writers in the the business.

For a full overview of the pandemic vaccine issue, I can think of no better resource than Maryn's 7 part series:

THE PANDEMIC VACCINE PUZZLE

Part 1: Flu research: a legacy of neglect
Part 2: Vaccine production capacity falls far shortPart 3: H5N1 poses major immunologic challengesPart 4: The promise and problems of adjuvantsPart 5: What role for prepandemic vaccination?Part 6: Looking to novel vaccine technologiesPart 7: Time for a vaccine 'Manhattan Project'?Bibliography





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