A patch for flu vaccine production

While we are all waiting for the other shoe to drop and a nasty, rip roaring flu pandemic to come rushing down the tracks at us, lots of companies have jumped into the pandemic vaccine sweepstakes. Reuters reports that at least 16 companies are testing flu vaccines and probably even more are involved in some technical aspect of vaccine production. That's good, although whether it will make any significant difference except around the margins remains to be seen. Timing is everything.

Meanwhile, though, work is going forward on many vaccine fronts. The one to hit the PR wires today is a report that Iomai Corporation out of Maryland has shown in a small human trial involving 500 people that combining their adjuvant skin patch with a single injection of containing 45 micrograms of H5N1 antigen is sufficient to stimulate a level of antibody considered protective in 70% of the subjects. Whether that level is too high, too low, just right or irrelevant we won't know until the balloon goes up, but that's a problem all the vaccines have -- testing to see if they would really work in the real world infections. The big advance here is that unlike other schemes, this one involves only one injection. The 45 microgram injection requires much more antigen than some competitors, but it is really equivalent to two 22.5 microgram injections and only has to be given once, a tremendous advantage in a pandemic setting. The only licenses pre-pandemic H5N1 vaccine in the US has 90 micrograms of antigen and has to be given twice.

The patch is applied to a the subject's skin after it has been lightly abraded with a sandpaper like material. The patch itself has 50 micrograms of some material (not identified in the news reports) and was tested with an egg-based vaccine, but the company says they believe it could be used with other vaccines after suitable testing. They also claim the patch has a 2-year shelf life (and so could be stockpiled) and "treavels" well. These are essential characteristics for practical distribution and use in a crisis.

What are some of the other vaccine problems that various people are trying to solve? Antigen-sparing technologies, like adjuvants (non-vaccine additives that boost the immune response when given with the vaccine) is one big area, and the patch is a version of this. But another important effort is to try o get away from egg-based vaccines. There aren't enough eggs, not enough production facilities, not enough time. There is a lot of work on this now, commonly involving growing viral antigen in tissue culture or bacteria. This has the potential for much faster turn around after a pandemic strain has been identified, a faster production ramp up and easier scale up and even replication and dissemination of small production facilities. Other work focusses on trying to find the Holy Grail of flu vaccines, a vaccine that works across all strains and subtypes -- the universal flu vaccine.

This is a crowded and competitive field. No one knows if there will be enough time to figure out something that is safe, effective and feasible.

And even if there were enough time, how would we vaccinate the population when we have a broken down and failing public health system? Ah, that's still another problem. Unfortunately it's not one we are working on.

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"Life has no price". That's not true. It's costly to survive during a pandemic, especially for the insolvent "third world".

One minor dissent.... we have argued against the over-reliance of mass vaccination clinics, which have been set up and practiced for the smallpox mass vaccination event that never happened (civilians refused, based on lack of credible rationale - it succeeded only in the military).

But mass vaccination clinics are still being practiced and drilled, and that's how the population would be vaccinated. The visiting nurses in your area would be heroes.

That doesn't come close to solving other PH infrastructure issues or that which needs to be rebuilt (mass vac clinics are jerry-rigged solutions), but that, at least, IS being worked on.

To have vaccines it's an opportunity , to plan how to manage them to cover a maximum of people it's better. It's only a question that the government wants to invest in the American Public Health. The "Health" is not quite "public" in USA.

Avian influenza A/H5N1 presents a serious and possibly imminent pandemic threat. The clinical trial results reported by Iomai suggest its patch technology might eventually become useful for global vaccination (no requirement for needles and syringes and probably no need for a vaccine cold chain), but thus far this approach has not been shown to be antigen sparing. If today the world had to depend on conventional adjuvanted inactivated H5N1 pandemic vaccines, all vaccine companies could produce in a six-month period (i.e., approximately 9 months after the emergence of the pandemic virus) enough doses of vaccine to vaccinate with two doses about 750 million people. This number is less than the combined populations of the nine major vaccine producing countries. Recently, Tamiflu resistance has cropped up in seasonal H1N1 viruses and this development has led to concern that similar resistance could develop in a future pandemic virus. More important, outside of the nine major vaccine-producing countries, government stockpiles of Tamiflu are sufficient to treat about 1% of the world's people who live in "have not" countries that don't produce influenza vaccines. At a recent scientific meeting in Singapore, investigators reported that among people in Indonesia who had been infected with the clade 2 H5N1 virus, 33/33 (100%) of those who received no antiviral treatment died. It is not difficult to imagine that if this virus were to evolve into a human pandemic virus, we could see a global population die off. Timely supplies of affordable vaccines and antiviral agents to confront such a virus will be unavailable to most people in the world.

Given the overwhelming need for effective alternatives for pandemic treatment and prophylaxis, generic agents that target the host immune response or the pandemic virus should be considered. Many influenza scientists doubt these agents would be effective. Nonetheless, several retrospective studies suggest that statins improve outcomes in patients with bacteremia and pneumonia and might be similarly effective against influenza. A preliminary report of results from a randomized controlled trial of ICU pneumonia patients showed that statin treatment reduced hospital mortality by 50%. An experimental study has shown that the fibrate gemfibrozil, a PPARα agonist, reduced mortality in H2N2 influenza virus-infected mice by 54%. There is considerable molecular cross-talk between statins and PPAR agonists, and their clinical effects are additive in patients with cardiovascular diseases. Chloroquine increases endosomal pH, impairing influenza virus release into the cytosol. Resveratrol, the polyphenol found in red wine, reduces influenza mortality in experimentally infected mice. All of these agents - statins, fibrates, chloroquine and resveratrol (and several other agents) - are produced as generic medications in developing countries. They are inexpensive, could be stockpiled and would be available on the first pandemic day. Given the lack of realistic alternatives for confronting the next pandemic, we cannot afford not to undertake the research needed to determine whether these and other generic agents could mitigate the effects of what might otherwise become an unprecedented global public health crisis.

By David Fedson (not verified) on 21 Mar 2008 #permalink

sorry, but why is vaccine production in a pandemic limited ? (by factors other
than just money)
Earlier they said hens can't lay more eggs, now we have cell-based vaccine which was
supposed to solve this.
Well, capacities are limited by the number of bioreactors,
workers and such,
but these can quickly be enlarged in an emergency.
Just some additional costs. Or not ??

I don't understand quite why there has been no scientific data forthcoming to the world's medical scientific community proving that influenza vaccine works...other than a few subjective anecedotal studies.

There is also no data indicating that current antivirals work other than anecdotal opinion as well. Since the vast majority of patients now recieve antivirals and there have been relatively few cases, I don't quite now how the conclusion can be reached they are effective given the mortality rate...which by the way, last time I looked, was increasing.

Considering all of the other medications that have recently been proven to do more harm then good, I think at this point a little proof would be in order...don't you think?

On the other hand...vaccines against secondary bacterial pneumonia do work...and are cost-effective unlike the current questionable seasonal influenza vaccine.

Tom: You keep perseverating about this. We've discussed the studies -- including actual clinical trials. The reason you can't understand it is that you continually ignore what there is. What constitutes "proof" in your book?


Sorry for Perservating...never heard of the term out here in the country. /:0)

If the dike won't hold an inch of rain...then it is unlikely to hold a foot...and it seems as the days go by...there is growing subtle indication that current vaccines and antivirals don't work for the 'inch' of rain...seasonal influenza.

For example, if there is already substantial resistance of current antivirals to seasonal influenza, given their recent introduction and minor amounts of usage...why would we believe that they would be effective...at all...in the supernatural virulent currents of an H5N1-influenced pandemic.

The writing seems on the wall for all to see...especially given the early requirement to double the dosage in an attempt to make "a silk purse out of a sow's ear".

I also do not think that it is by coincidence that we are seeing improvement in virulence of seasonal strains...in an environment of ever increasing vaccination rates in the population.

As you would know...I am quite sure...there are potentially more downsides to a partially effective vaccine in the field then upside...and accentuated and artificially accelerated evolution of the virus is just one.

For example...what do you think of:


The question asked would by why does it work in lab experiments with laboratory animals and then not in the field...this has been a relatively common event in the animal world in the past.

The answer is that researchers freeze-frame the virus in the lab so that it is not allowed to naturally circulate and evolve in an animal population in natural 'antigenic drift' away from the vaccine...

...so in the artificial condition of no evolution...the vaccine works...but that only works if we all live in individual bubbles isolated away from the population.

Here are some things that will work in a pandemic. food, water, antibiotics, maybe statins, anti-shock therapies, anti-fever remedies, secondary baterial vaccines (where a lot of the killing occurs anyway)...and telephone support to give advise to (rightly) worried young parents etc.

Here are three things that won't work in a pandemic (especially one a fraction as lethal as H5N1 - unfortunately): vaccines, antivirals, hospitals and person to person professional healthcare.

If you have provided the proof, I must have missed it.

Thanks and as always, this is meant to be constructive rather than destructive.

Sorry...forgot to mention...and Thanks gs for the wikipedia information.

...and by the way...those who think that an H5N1 pandemic won't happen because it hasn't...don'tunderstand nature and animal-related disease emergence very well.

H5N1 is following a well-worn path...and with my limited experience...I have not seen one get this far and not finish the job...unfortunately.