Disaster/Pandemic preparedness

indigo girl · Oct 31, 2007

The Pandemic Vaccine Puzzle

Part 4: The promise and problems of adjuvants

Maryn McKenna Contributing Writer

"Editor's note: This is the fourth 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 3 discussed the immunologic challenges posed by the H5N1 virus, including its poor immunogenicity when incorporated in vaccines and the difficulty of assessing immune responses to the vaccines."

http://www.cidrap.umn.edu/cidrap/content/influenza/panflu/news/oct3007panvax4.html

Adjuvanted vaccines appear to hold the greatest promise for solving the grave supply-demand imbalance in pandemic influenza vaccine development. They come with obstacles--immunologic, regulatory, and commercial--but they also have generated more excitement than any other type of vaccine thus far.
In an example of the hope being hung on adjuvants, the WHO last week issued a statement declaring that the pandemic vaccine supply is "sharply" increasing and forecasting that annual manufacturing capacity will rise to 4.5 billion two-dose courses by 2010.... based on the expectation that flu vaccines made in 2010 will include an adjuvant permitting the use of just one-eighth of current vaccines' antigen content. (Adjuvants are chemicals that are incorporated in some vaccines to improve response to the vaccines' active ingredient. Adjuvants make it possible to reduce the dose of antigen in a vaccine without dampening the immune response.)
...they are by definition immune-system activators. ...few have entered the market, because they proved too reactogenic to be acceptable to consumers or safe.Only...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...
No adjuvanted flu vaccine is licensed in the United States--a notable oversight since federal health authorities urged such a vaccine be investigated as a preparedness measure after the pandemic of 1957...Fifty years later, the need to seek regulatory approval for novel components in adjuvanted pandemic vaccines could prove a barrier to rapid market entry of formulas that look promising.
Like many other aspects of pandemic planning, adjuvants' ability to solve some of the challenges of preparedness will depend on how rapidly a pandemic arrives.
...(FDA) has indicated that pandemic vaccines made in the same manner as an already-licensed seasonal vaccine may be treated only as a "strain change," in an accelerated approval process by which components are swapped out of existing seasonal flu vaccines each spring.
But since there are no adjuvanted seasonal flu vaccines currently licensed in the United States, antigen-sparing pandemic vaccines may require a full Biologics License Application--the complete portfolio of testing and data, on both the product and the manufacturing facility, that is demanded of any new drug submitted for licensure and can take years to assemble...
...adjuvants can be brought forward only as part of a precise antigen dose/adjuvant combination that must be tested for safety and efficacy, probably in a "non-inferiority" trial against the same antigen dose without adjuvant, and then submitted for licensure...
There is currently no regulatory pathway by which adjuvants may be submitted for approval as products by themselves--or may be paired with a separately manufactured antigen, perhaps one produced by another company.
"There probably are more concerns about an antigen made with one manufacturing process and an antigen made with another manufacturing process and whether when those are mixed with ideal adjuvant X in two potentially different circumstances or time points, that could raise a bunch of issues about formulation, stability, immunogenicity, safety"...

indigo girl · Oct 31, 2007

Want to know more about adjuvants? SophiaZoe has some interesting

commentary. She has also provided links to some posts by Susan C at Fluwiki.

For those of you that do not know, Susan C is one of the editors at Fluwiki. My

understanding is that she is a physician living in the UK, and that she

used to work for the CDC. If this is not correct, I am sure that someone

will let me know and I will correct the information.

At any rate, this infomation about adjuvants, vaccine trials, and product testing is eye opening.

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

indigo girl · Nov 1, 2007

THE PANDEMIC VACCINE PUZZLE

Part 5: What role for prepandemic vaccination?

Maryn McKenna Contributing Writer

"Editor's note: This is the fifth 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 4 examined the possibility of using adjuvants to stretch the supply of pandemic vaccines and the regulatory barriers to that strategy."

http://www.cidrap.umn.edu/cidrap/content/influenza/panflu/news/oct3107panvax5.html

Experiments with vaccine adjuvants have raised some hope of removing one of the great stumbling blocks to pandemic influenza preparedness: the impossibility of making a vaccine that protects against a pandemic virus before that virus actually emerges.
A number of the studies that have shown adjuvants may be able to stretch the vaccine supply also demonstrated a secondary benefit: The formulas protected not only against the H5N1 flu strain on which they were based, but against other H5N1 strains as well, a phenomenon called cross-reactive protection.
... that could allow production of at least partially protective vaccines well in advance of a pandemic's beginning.
...the lag time to the pandemic's emergence might be so long that the vaccination would seem pointless. As well, the vaccine might cause a greater-than-expected rate of adverse events, causing both direct harm to recipients and indirect damage to government credibility--results that would be particularly difficult to tolerate if vaccination proved unnecessary because the pandemic did not arrive. Those risks are not theoretical: They have been demonstrated in the United States twice in recent history, in the abortive 2002 smallpox vaccination campaign and the 1976 swine-flu campaign...
"...Would receipt of a vaccine prepared before the pandemic be effective in providing some protection or in priming recipients so a single subsequent dose of vaccine would be protective?"
The most likely and biologically plausible use of prepandemic vaccination would be as the first half of a "prime-boost" series. People would still be given the two doses of vaccine necessary to provoke immunity in a naïve individual.

But the doses would be based on different vaccine strains--the first an early best guess, the second tuned to the pandemic strain--and could be given not weeks but months or years apart if the science supported it.
To achieve prepandemic vaccines, researchers would have to ascertain the right dose and dose interval, determine how long priming lasts, and solve the puzzle of measuring primed immunity.
Further, regulatory authorities would have to determine the trial design that could deliver those answers, the public discussion that would be necessary for prepandemic vaccines to be accepted, and the safety data that would need to be gathered once the vaccines went into use...
Recognizing those hurdles, the European Centre for Disease Prevention and Control said in August that while it welcomes
the development of prepandemic vaccines, it would not support administering them until a WHO declaration of pandemic phase 5 or 6, meaning significant human-to-human transmission is occurring or a pandemic is under way...

indigo girl · Nov 2, 2007

THE PANDEMIC VACCINE PUZZLE

Part 6: Looking to novel vaccine technologies

Maryn McKenna Contributing Writer

"Editor's note: This is the sixth 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. Part 5 looked at the idea of vaccinating people before a pandemic with a best-guess vaccine and following up later with a vaccine matched to the emergent pandemic strain."

http://www.cidrap.umn.edu/cidrap/content/influenza/panflu/news/nov0107panvax6.html

Frustration with the slow pace of pandemic-vaccine achievement has spurred second looks at both old and new technologies, such as using whole influenza viruses instead of fragments or growing flu viruses in cultures of mammalian cells instead of in eggs.
Such approaches may yield cross-protection against various H5N1 strains, shorten the production timeline, or increase the amount of vaccine that can be produced.
Live-attenuated vaccine has been...struggling for market share since it was introduced in 2003 by MedImmune
Because they contain live virus, live-attenuated vaccines provoke multiple types of immunity.
In studies they have been shown to protect against both the strains from which vaccine candidates were derived and against drifted (slightly mutated) strains as well--characteristics that make them highly appealing to pandemic planners ...
They also grow in eggs at a much higher volume than inactivated vaccines...
But their live-virus content is responsible for the vaccines' greatest potential danger: the possibility that they might lead to reassortment between the vaccine virus and circulating flu strains.
Intradermal vaccination appears to provoke acceptable levels of immunity while using only 20% to 30% of the standard intramuscular dose--but the injection technique is more challenging and may not be feasible for mass vaccination programs that might use less-trained volunteers...
...academics from the University of Hong Kong recommended...giving lower-than-planned doses of vaccine during a pandemic, arguing that vaccinating more people with a reduced dose could create a mass effect large enough to slow down spread of the disease..."We must . . . consider whether anyone is ready for the potential consequences of deploying a suboptimal vaccine in an uncertain attempt to maximize our herd protection, with a possible reduction in the extent of protection of individuals"...
Moving flu vaccine production from eggs to cell culture would...free manufacturers from the necessity of procuring enough eggs up to a year in advance.
By dispensing with eggs, it would eliminate the need for putting a pandemic virus through reverse genetics, shaving 4 to 6 weeks off vaccine production.
And because the vaccine virus is grown in giant industrial fermenters, it could offer a vast increase in production capacity--but only if manufacturers or governments make significant capital investments or manufacturers quickly convert the 2.5 million liters of cell-culture capacity ... in use around the world for other pharmaceutical products
... isolating the flu virus's hemagglutinin gene and using recombinant technology to express the hemagglutinin in insect cells grown in bioreactors... can halve the standard production timeline while delivering higher yields...
...a universal vaccine.... "The optimal long-term solution to pandemic vaccination is the development of a new influenza vaccine against an antigen that is present in all influenza subtypes and does not change,"... So far, however, vaccines based on conserved regions of the virus such as the M2 protein have shown only the ability to reduce disease, not to prevent infection...

indigo girl · Nov 4, 2007

THE PANDEMIC VACCINE PUZZLE

Part 7: Time for a vaccine 'Manhattan Project'?

Maryn McKenna Contributing Writer

"Editor's note: This is the last 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. Part 6 explored the potential of novel vaccine technologies such as using whole flu viruses or growing vaccines in cell cultures instead of in eggs."

http://www.cidrap.umn.edu/cidrap/content/influenza/panflu/news/nov0207panvax7.html

"If we are serious about a pandemic, we should assume it is going to be imminent and we should be prepared as if it is imminent--not 10, 15 years down the road, but imminent," said David Fedson, MD, a retired vaccine industry executive who has published analyses of pandemic vaccine planning ...
Former Senate Majority Leader William H. Frist (R-Tenn.) called in August 2005 for a "Manhattan Project for the 21st century"... In the same month, Michael T. Osterholm, PhD, MPH, director of the University of Minnesota Center for Infectious Disease Research and Policy, publisher of CIDRAP News, recommended the creation of "an international project to develop the ability to produce a vaccine for the entire global population within several months of the start of a pandemic [that would be] a top priority of the Group of Seven industrialized nations plus Russia (the G-8)"...
...Trust for America's Health recommended in October 2006 that governments create a "multinational pandemic vaccine research and development master program" ...recommending an appropriation of $2.8 billion in such a project's first year (see Bibliography: IDSA 2007).
"An effort on the scale of the Apollo space project is required," the IDSA said.
It requires active coordination among all the federal health agencies along with cooperation from congressional funders, plus parallel efforts in other countries.... it is a global public health problem that requires better management"...
...it is urgent that such an effort be established soon, because there is no way of predicting accurately when a pandemic might arrive. If it arrives soon rather than later, the lack of vaccine in most of the world will create a divide between haves and have-nots that could corrupt international relations long after the pandemic ends.
The long standoff with the Indonesian government over sharing of H5N1 isolates has provided a foretaste of the disruption such resentment could cause. The health ministry of Indonesia--the country that has experienced the most human cases and deaths from H5N1 flu--stopped sending isolates to World Health Organization (WHO) collaborating laboratories in late 2006. Those laboratories both analyze the isolates to track the evolution of seasonal and novel flu strains and use them to develop pandemic vaccine candidates; Indonesia's decision to stop contributing was apparently triggered by the realization that it could never afford to purchase vaccines made from isolates it provided.
"At this point, when a pandemic happens, vaccines are going to provide some benefit to a very limited number of people," Osterholm said. "But they are also going to create a major diversion of activity and energy when the decisions have to be made about who gets what limited vaccine exists. I worry that their negative impact will outweigh their positive impact: They will cause a crisis of leadership around the world" (see Bibliography: Osterholm 2007).

indigo girl · Nov 5, 2007

readymoms respond

this is worth reading. these people really are heroes.

http://afludiary.blogspot.com/2007/11/readymoms-respond.html

we are parents concerned about the potential impact of the next pandemic on children, families, and communities.
we are especially concerned about the following:
1. if a 1918-like pandemic happens today, communities will suffer 20 years of normal child deaths (aged 1-19) in the space of one season.
2. the current h5n1 avian influenza virus is causing human infections with an overall case fatality rate (cfr) of 60%.
3. this cfr rises to 75% for those aged 10-19.
4. h5n1 has to become 30 times (not 30%) weaker to match the 2% cfr of the 1918 pandemic.
5. a who working group report in 2006 tells us that "the present high lethality could be maintained during a pandemic" caused by h5n1.
we believe parents have a right to be given this information, and be supported to make the decisions that are best for their family.
we believe that failure to assist families to make informed choices will result in severe social disharmony as bereaved parents take their wrath against officials who have failed them.

we believe it is possible to protect our families with adequate implementation of the social distancing measures as specifically recommended by the cdc, especially early and proactive school closure.
we believe these same measures will also make it safe for essential workers to go to work.
we understand that implementation of these measures will require communities to make some tough choices between the cost to the economy and saving lives.
we believe that such choices cannot and should not be made for families and communities, only by them.
we fully agree with the following sentiments expressed by this participant at the cdc community mitigation stakeholders' meeting (atlanta, december 2006).
"the question of how much this will cost is the wrong question. the correct question is what is the price we are willing to pay? i would sacrifice everything i own to save one of my kids - everthing. and i would consider it the best bargain of my life.

http://afludiary.blogspot.com/2007/11/update-on-readymoms-at-apha-expo.html

indigo girl · Nov 7, 2007

Updated: Citizen's Guide To Pandemic Preparedness

http://afludiary.blogspot.com/2007/11/updated-citizen-guide-to-pandemic.html

With a forward by David Heymann, Deputy Director-General
World Health Organization, and input from Dr. Grattan Woodson on the home treatment of Influenza, this guide is an excellent introduction to pandemic preparedness.
This download is being hosted by the Flu Wiki. The guide itself is a product of the Mid-Peninsula (San Francisco Bay area) Citizens Preparedness Committee

The Impact of a Pandemic
Overview
* Communities will be affected simultaneously.
* At least 30% of the overall population will
become infected.
* Absenteeism is expected to be upwards of 50%.
* A pandemic is likely to last for 12 to 18 months.
* Communities could be affected by several waves
lasting 6 to 8 weeks each.
* Vaccines and antiviral drugs for pandemic
influenza will be in short supply, may be of limited
effectiveness, and are not likely to be available to
most communities.
* Most of the ill will seek medical care.
* All healthcare systems will be overwhelmed.
* Health facilities are unlikely to be available to
most, and may be inadvisable to enter owing to
increased chances of exposure to the virus.
* People and communities will likely be on their
own without the help of mutual aid from other
communities, hospitals, or other public services.

* Those who take steps to prepare ahead of time
will be much more resilient as pandemic influenza
spreads .

indigo girl · Nov 9, 2007

Utah Pandemic Flu Commercial

I am having a hard time believing that they are showing this. A year ago,

nothing and now they are finally trying to get thru to people with PSAs

like this.

http://afludiary.blogspot.com/2007/11/video-utah-pandemic-flu-commercial.html

UPDATE

Apparently the intensity of the message is making some people uncomfortable but it does serve the purpose

of getting the public attention, at any rate further PSAs are planned that are more geared to educating

people to prepare themselves:

http://www.flutrackers.com/forum/showpost.php?p=107899&postcount=1

sharona97, BSN, RN · Nov 9, 2007

Wow, someone is finally taking the lead, let's hope it catches on state to state. Thanks Indigo Girl.

indigo girl · Nov 10, 2007

Local Wal-Marts Promote Pandemic Awareness

We need to see more of this with local businesses working with hospitals and and

health departments helping the public to prepare in the most basic way by

putting away food and essentials that families will need.

http://www.flutrackers.com/forum/showpost.php?p=108183&postcount=1

The Granger resident's mom, Laurie Farris, was the one who entered a contest at the Mishawaka Wal-Mart store to win a pandemic flu kit. She called her daughter to pick up the winnings because she was out of town at the time.
The St. Joseph County Health Department along with other community groups developed the idea of giving away pandemic flu supplies to raise awareness about a possible epidemic.
All St. Joseph County-area Wal-Marts participated in the contest.
The conclusion of the local pandemic flu event came on the heels of a new national study revealing how little prepared children are when it comes to the virus.
The recently released report by the American Academy of Pediatrics and Trust for America's Health showed that children and teens account for nearly 46 percent of all bird flu deaths.
"How to treat and care for the nation's 73.06 million children and adolescents during an influenza pandemic is a significant concern," the report reads.

indigo girl · Nov 11, 2007

How Much Tamiflu Is Enough?

Avian Flu Diary takes on the Tamiflu dosage controversy with very clear

commentary on why this is such a problem:

http://afludiary.blogspot.com/2007/11/how-much-tamiflu-is-enough.html

Today's story out of the UK indicates that their Pandemic Influenza Scientific Advisory Group is urging the government to triple their stockpile of Tamiflu (oseltamavir).
They believe that coverage for 75% of their population is essential if they are to "exert reasonable control over the scale and severity of the national outbreak"

The latest research by the Pandemic Influenza Scientific Advisory Group claims that the number of antiviral doses held by the Government must be tripled if a flu pandemic is to be effectively controlled.
The current stockpile of 14.6 million courses of the antiviral drug Tamiflu covers 25 per cent of the population.
... the scientists recommend boosting the stockpile to cover more than 75 per cent of the population.

sharona97, BSN, RN · Nov 12, 2007

Did I miss something? I thought Tamiflu was ineffective in survival for the H5N1 strain. If so why the discussion on stockpiling or increasing the dosage amount?