Disaster/Pandemic preparedness

indigo girl · Oct 26, 2007

http://www.cidrap.umn.edu/cidrap/content/influenza/panflu/news/oct2507panvax1.html

THE PANDEMIC VACCINE PUZZLE

Part 1: Flu research: a legacy of neglect

Maryn McKenna Contributing Writer

"This is the first in a seven-part series investigating the prospects for development of vaccines to head off the threat of an influenza pandemic posed by the H5N1 avian influenza virus. The series puts advances in vaccine technology in perspective by illuminating the formidable barriers to producing an effective and widely usable vaccine in a short time frame."

It has been 10 years since the H5N1 strain of avian influenza first grabbed international attention by causing the death of a Hong Kong 3-year-old, the novel virus's first known human casualty (see Bibliography: CDC 1997). In the decade since, the virus has torn across the globe, causing 332 known human illnesses and 204 deaths in 12 countries, according to the World Health Organization (WHO), as well as the deaths or preventive slaughter of hundreds of millions of birds.
In that time, avian flu and the potential human pandemic it could cause have waxed and waned in public attention. Scientific attention to the H5N1 threat, though, has never wavered. Much of that attention has focused on finding a vaccine against H5N1, "the single most important public health tool for decreasing the morbidity, mortality and economic effects of pandemic influenza," according to Dr. Gregory Poland, director of the Mayo Clinic's Vaccine Research Group in Rochester, Minn.
...after almost a decade of research, a safe, effective, affordable, and abundant vaccine against H5N1 flu remains disappointingly out of reach. The search for a human avian-flu vaccine that could be developed and delivered in time to short-circuit a pandemic has been dogged by multiple obstacles across many sectors.
... As the WHO admitted in its Global Pandemic Influenza Action Plan, published last year, "At the present time, if an influenza pandemic were to occur, the potential vaccine supply would fall several billion doses short of the amount needed to provide protection to the global population"

indigo girl · Oct 27, 2007

Pig farmers encouraged by CDC to get flu shots

http://www.curevents.com/vb/showpost.php?p=813821&postcount=94

... pig farmers are specifically being encouraged to get the shot to protect themselves and those around them since they could spread the flu to their livestock.
According to the Centers for Disease Control and Prevention Web site, pigs can be infected with both human and avian influenza viruses in addition to swine influenza viruses.
Getting the flu shot is one way for producers to reduce the risk of bringing the virus to the farm.
...the CDC site states that one pig could potentially get infected with influenza viruses from more than one species at the same time. If that were to happen, the genes of the viruses could mix and create a new virus.
And if the original two viruses happened to be the human influenza virus and the avian influenza virus, for example, the result could be that the infected pig could infect humans and the new virus could spread from one person to the next. The CDC reports that humans might have little or no immunity to such a virus, meaning that it could lead to an influenza pandemic.
In addition to the flu shot, Wagstrom recommends other practices to reduce infection of pigs with human influenza viruses. Among them is having sick-leave policies that encourage workers to stay away from the farm if they are suffering from acute respiratory infections. She also suggests good building ventilation and good hygiene to reduce transmission of the flu viruses.

http://www.recombinomics.com/News/10250702/H1N1_Swine_Seasonal.html

...Human seasonal flu sequences from patients infected with H1N1 earlier this year have a number of swine polymorphisms in multiple gene segments. These acquisitions signal dual infections involving human and swine influenza.
The acquisitions were supported by recently released swine sequences collected between 2005 and 2007 throughout the United States.
The movement of human influenza into swine, as well as swine influenza into humans is cause for concern. The human sequences in swine evolve more slowly and acquire swine polymorphisms. These infections can act as a reservoir of early human as well as swine polymorphisms which can move into seasonal flu via recombination. Similarly, the acquisition of human polymorphisms in swine increases regions of identity, which can facilitate additional recombination.
The 1918 pandemic H1N1 was a recombinant with human H1N1 and swine H1N1 sequences, which raises concerns about the increased movement of swine and human sequences between the two species.

indigo girl · Oct 27, 2007

THE PANDEMIC VACCINE PUZZLE

Part 2: Vaccine production capacity falls far short

Maryn McKenna Contributing Writer

"Editor's note: This is the second in a seven-part series investigating the prospects for development of vaccines to head off the threat of an influenza pandemic posed by the H5N1 avian influenza virus. The series puts promising advances in vaccine technology in perspective by illuminating the formidable barriers to producing large amounts of an effective and widely usable vaccine in a short time frame. Part 1 described how flu research has been a relatively low priority until very recently, which has left many important scientific questions unanswered."

http://www.cidrap.umn.edu/cidrap/content/influenza/panflu/news/oct2607panvax2.html

...achieving a widely deployable pandemic vaccine is currently out of reach... The world lacks the manufacturing capacity to make enough vaccine to matter.
A vaccine-industry scenario, described in August in the journal BioPharm International, goes out 6 months...adding up to a vaccine product that would arrive roughly in time for the pandemic's second wave but long after the first patients had recovered or died
But the more difficult obstacle is not the time needed to produce vaccine...but the amount of vaccine needed.
... a pandemic vaccine would need to be given twice, because, unlike with seasonal flu, there would have been no prior exposure to the novel strain. So absent the use of adjuvants to stretch limited antigen supplies, industry could produce at best enough vaccine for 750 million people, far short of the amount needed to cover the world's 6.7 billion inhabitants
The WHO analysis hides a number of highly optimistic assumptions, including zero glitches in production and 100% cooperation by regulators.... It is...likely that vaccine would never leave the countries where it is produced.
The WHO action plan avers that manufacturers will significantly expand production capacity by 2012, largely because demand for seasonal flu vaccine will rise--but it offers no evidence that demand can be stimulated to levels that will persuade manufacturers to invest
The WHO plan asks countries that do not now use seasonal flu vaccine to launch new seasonal vaccination campaigns as a way of stimulating demand. It also asks countries with existing vaccination programs to increase vaccine use, so that 75% of those for whom vaccination is recommended are taking the shot
Creating enough vaccine-manufacturing capacity to protect the world's population is not cheap. The price tag is likely to be at least $2 billion and could rise to $9 billion... Experts within the vaccine industry say that expecting manufacturers to make the investment asks companies to spend against their own best interest.

While vaccine manufacturers are likely grateful for the HHS funding, others in the industry say the investment is incomplete--because it does nothing to expand capacity for critical downstream tasks such as bottling and administering completed vaccine.
"You have to think about every part of the components," Lysfjord said. "The machines, the plants, the chemicals; the stopper, the glass, the aluminum overcast for the top of the vial; the labels. You're not aware of how well-connected the system is until it breaks, and it is going to break big-time."

Editorial Team / Admin · Oct 27, 2007

indio girl.....

...achieving a widely deployable pandemic vaccine is currently out of reach... the world lacks the manufacturing capacity to make enough vaccine to matter.

.....how many manufacturer's are there now worldwide? i know the u.s. has at least 5, is that correct? (do they supply the world as well??)

... a pandemic vaccine would need to be given twice, because, unlike with seasonal flu, there would have been no prior exposure to the novel strain. so absent the use of adjuvants to stretch limited antigen supplies, industry could produce at best enough vaccine for 750 million people, far short of the amount needed to cover the world's 6.7 billion inhabitants

i'm sure this information is not common knowledge. thank you for the continued updates.

mcmike55 · Oct 27, 2007

All real good suggestions, good posting as well. With the fires in California, a timely topic as well.

I have a suggestion for all you good folks, take CERT training.

CERT, Community Emergency Response Team training is done through the EMA in your area, and teaches basic medical operations, fire suppression, disaster psychology, and search and rescue.

The idea is to teach you how to first, take care of yourself and your family in the time of an emergency, then if possible, how to go out and help your neighbors.

I teach the classes here in SouthEast Ohio, and really think they are great, not only for nurses, but fire, EMS, or any citizen.

Check out your local EMA, or go on line and search CERT or try the Home Land Security website.

Mike

indigo girl · Oct 27, 2007

....How many manufacturer's are there now worldwide? I know the U.S. has at least 5, is that correct? (do they supply the world as well??)

Thanks, sirI, and thanks to CIDRAP for this series.

Who makes the flu vax that you are using?

If we are talking strictly flu vax, all I am hearing about is Sanofi Pasteur in

Swiftwater, Pa, and I think that FluMist by Medimmune is out of Gaithersburg, Md(?). I could be wrong about that one, but I think they have a plant in the US.

Novartis has broken ground for a plant in North Carolina.

Anyone else know of any flu vax producing plants actually on US soil?

CIDRAP is correct. The US is at disadvantage in this respect.

The following have plants outside the US:

Baxter

Chiron

Medimmune + AstraZenica

Aventis Pasteur

Acambis

Wyeth

(Thanks to Ayerman, andPFI/pixie,JWB,UKbird for this list)

indigo girl · Oct 27, 2007

All real good suggestions, good posting as well. With the fires in California, a timely topic as well.
I have a suggestion for all you good folks, take CERT training.
CERT, Community Emergency Response Team training is done through the EMA in your area, and teaches basic medical operations, fire suppression, disaster psychology, and search and rescue.
The idea is to teach you how to first, take care of yourself and your family in the time of an emergency, then if possible, how to go out and help your neighbors.
I teach the classes here in SouthEast Ohio, and really think they are great, not only for nurses, but fire, EMS, or any citizen.
Check out your local EMA, or go on line and search CERT or try the Home Land Security website.
Mike

An excellent suggestion. Thank you.

Editorial Team / Admin · Oct 27, 2007

Thanks, sirI, and thanks to CIDRAP for this series.
Who makes the flu vax that you are using?
If we are talking strictly flu vax, all I am hearing about is Sanofi Pasteur in
Swiftwater, Pa, and I think that FluMist by Medimmune is out of Gaithersburg, Md(?). I could be wrong about that one, but I think they have a plant in the US.
Novartis has broken ground for a plant in North Carolina.
Anyone else know of any flu vax producing plants actually on US soil?
CIDRAP is correct. The US is at disadvantage in this respect.
The following have plants outside the US:
Baxter
Chiron
Medimmune + AstraZenica
Aventis Pasteur
Acambis
(Thanks to PFI/pixie,JWB,UKbird for this list)

CSL Ltd out of Australia is providing the U.S. with Afluria (a fast-tracked vax): http://www.medicinenet.com/script/main/art.asp?articlekey=84217 . This makes the 6th manufacturer, but not on U.S. soil.

We use FluMist (yes, they are out of Maryland). And, Fluzone.

AnneZ · Oct 27, 2007

...achieving a widely deployable pandemic vaccine is currently out of reach... The world lacks the manufacturing capacity to make enough vaccine to matter.

.....How many manufacturer's are there now worldwide? I know the U.S. has at least 5, is that correct? (do they supply the world as well??)

..

. a pandemic vaccine would need to be given twice, because, unlike with seasonal flu, there would have been no prior exposure to the novel strain. So absent the use of adjuvants to stretch limited antigen supplies, industry could produce at best enough vaccine for 750 million people, far short of the amount needed to cover the world's 6.7 billion inhabitants

I'm sure this information is not common knowledge. Thank you for the continued updates.

Influenza vaccine manufacturers

http://www.who.int/csr/disease/influenza/manulist/en/index.html

Baxter. Austria

France. Aventis Pasteur SA

Italy. Istituto Vaccinogeno Pozzi

Germany. GlaxoSmithKline

Germany. Chiron Vaccines

Italy. Chiron Vaccines

Japan. Denka Seiken Co. Ltd

Australia. CSL Limited

Canada. ID Biomedical

China. Beijing Tiantan Biological Products

China. Changchun Changsheng Life Sciences Ltd

China.Lanzhou Institute of Biological Products

China. Typharm

Japan. Chemo-Sero-Therapeutic Research Institute

Japan. Biken Research Foundation for Microbial Diseases of Osaka University

Japan. Kitasato Institute

Korea. Dong Shin Pharmaceutical Co

Netherlands. Solvay Pharmaceuticals

Netherlands. Crucell NV

Romania. Cantacuzino Institute

Switzerland. Berna Biotech Ltd

UK. Chiron Vaccines (there are 2)

US. MedImmune Vaccines Inc

indigo girl · Oct 27, 2007

Thanks, AnneZ, and flutrackers for the assistance.

I really did not know that there were this many vaccine

manufacturers. Alas, most not on US soil.

The following information is from monotreme at PFI, and I thank him also

for his contribution:

During a pandemic, seasonal flu vaccine plants will be converted to use for pandemic flu vaccine. Since the seasonal flu is trivalent, assuming equal amounts of antigen, flu vaccine supply would be triple current output during a pandemic. However, early H5N1 vaccines required very high levels of antigen to stimulate an immune response. And two immunizations would be needed. This would imply less flu vaccine available during a pandemic. OTOH, adjuvants like MF59 allow less antigen to be used to stimulate immunity, so less might be used.

http://www.reuters.com/article/governmentFilingsNews/idUSN1927223720070719

The vaccine arm of Sanofi-Aventis is the only U.S.-based producer of injectable flu vaccine. The plant will produce 150 million doses a year after the new 140,000-square-foot (13,000- square-metre) facility comes on line by 2010.

FluMist was based in Gaitersburg Maryland when it was made by MedImmune. MedImmune was bought by Astra-Zeneca. It appears to be produced in the UK. I'm not sure how much is actually produced in the US.

MedImmune says it resolves FDA FluMist plant issues

http://www.reuters.com/article/health-SP/idUSN0726177020070907

HHS Awards Two Contracts to Expand Domestic Vaccine Manufacturing Capacity for a Potential Influenza Pandemic

http://www.hhs.gov/news/press/2007pres/06/pr20070614a.html

indigo girl · Oct 28, 2007

Teaching Kids About Flu Prevention

As always, thoughtful commentary and useful information from SophiaZoe's

blog.

http://birdflujourney.typepad.com/a_journey_through_the_wor/2007/10/pandemic-influe.html

Two years ago, Geri Rodda wrote the 32-page children's health story "Lyme and in Rhyme" about Lyme disease. Both softcover books were published by Pumpkin Hill Productions, a small company in Hawleyville. MedImmune Inc. in Maryland (producers of FluMist vaccine) provided a grant to publish 1,000 copies of "The Flu and You."
The new 36-page book, with Crayola-style color pages, wild-haired cartoon characters and rhyming verse, is fun to read and provides a strong message on how to prevent and treat influenza. It is appropriate for children to read alone or for parents and grandparents to read aloud.

indigo girl · Oct 30, 2007

The Pandemic Vaccine Puzzle

Part 3: H5N1 poses major immunologic challenges

Maryn McKenna Contributing Writer

"Editor's note: This is the third in a seven-part series investigating the prospects for development of vaccines to head off the threat of an influenza pandemic posed by the H5N1 avian influenza virus. The series puts promising advances in vaccine technology in perspective by illuminating the formidable barriers to producing large amounts of an effective and widely usable vaccine in a short time frame. Part 2 discussed the huge gap between current global vaccine production capacity and the likely demand for vaccine in the event of a pandemic."

http://www.cidrap.umn.edu/cidrap/content/influenza/panflu/news/oct2907panvax3.html

...antigenic drift and division into clades, or subgroups, has already rendered some early vaccine candidates less potent against circulating strains.
...highly pathogenic, it must be handled initially in one of a relatively small number of high-biosecurity laboratories...
...requires the use of reverse genetics to create a seed strain that will reproduce in eggs.
Reverse genetics and the stringent pre-release testing that follows add a minimum of 6 weeks to the vaccine production process
...seed strain could be considered a genetically modified organism under European Union rules or a select agent under US law, further restricting the laboratories, personnel, and manufacturers who could work with it from then
on.
"Most manufacturers report that yields of antigen from reverse genetics-derived H5N1 viruses are 30-40% of the average of seasonal influenza viruses, reducing the quantity of antigen available for vaccine formulation
...when candidate vaccines have been produced from them, H5N1 and similar viruses have not done a good job of provoking an immune response.
...the best example of H5N1's poor immunogenicity is the 2006 trial that led to the first FDA licensing of an H5N1 vaccine. The trial... achieved acceptable levels of protection only at the highest amounts given, two doses of 90 mcg each, or 12 times the 15-mcg dose that induces immunity in a seasonal vaccine
Even at that dosage, only 54% or 58% of the subjects (by two different measures) exhibited antibody titers that matched FDA and CHMP regulations, compared with the 70% to 90% usually achieved with seasonal vaccine
The amount of antigen needed... is so high that the vaccine would stress the manufacturing system if put into broad production...
...the high dose--which at 180 mcg total is four times the total seasonal trivalent dose--could provoke an unusual rate of adverse reactions...
...the 90-mcg vaccine... will contain the still-controversial preservative thimerosal.
...our biggest scientific issue--that we are not sure what the appropriate surrogate for protection is, given the fact we have no ability to challenge [expose humans]...
...the FDA-accepted surrogate for immunity in flu-vaccine trials is a hemagglutination-inhibition (HI) antibody assay that returns a post-vaccination titer of more than 1:40 for 70% of those vaccinated ...But that measure is known to be imperfect even for seasonal flu:
.....Researchers have resorted to using a 1:40 result...
...It's important to understand that this choice of a 1:40 endpoint is not validated in any way as an actual assessment of protection against H5 in
humans...
The HI test may not return reliable results for vaccines that provoke types of immunity other than antibody response. That makes it an unreliable measure for the effectiveness of two promising alternative classes of vaccines: live-attenuated vaccines, which have the potential to generate immunity against multiple strains of flu, and inactivated adjuvanted vaccines (those containing a chemical immune-system stimulant), which could help solve the supply bottleneck by allowing much smaller amounts of antigen to be dispensed in each vaccine dose...