Swine flu vaccine: U.S. wouldn't have a shortage if it embraced enhanced version

The majority of Americans want to be vaccinated against swine flu, polls show. But unless you're in a high-risk group, such as expectant mothers, you may not get any vaccine anytime soon. In fact, the Centers for Disease Control and Prevention says the current tide of H1N1 influenza is likely to begin to ebb before the shortage of vaccine eases. Meanwhile, the toll from the virus keeps climbing, with deaths from H1N1 in the United States having likely reached 4,000, of which 540 are children.

There are several reasons for the worrisome vaccine shortage. The federal government ordered enough vaccine to immunize nearly the entire nation. But deliveries have been slow, to name one big problem. Perhaps more frustrating to many on the front lines of fighting the virus is that the shortage would ease considerably if the U.S. simply embraced an enhanced version of the vaccine. But so far, U.S. regulatory authorities -- unlike their counterparts in Europe -- haven't taken the steps to make this happen.
The Adjuvanted Vaccine

The enhanced, or adjuvanted vaccine as it's known, is a modified vaccine that boosts the immune system, allowing for even greater protection. Adjuvanted vaccines, used widely worldwide, are known to be dose-sparing vaccines. They use less vaccine material in one dose, which would allow the U.S. to stretch its supply of vaccine.

But because U.S. regulators have never approved these enhanced vaccines for use in the past, they're unlikely to be cleared for use in time to combat the pandemic. As a result, the nation is likely going to be able to vaccinate only a modest portion of the country before the full brunt of winter hits.

As it stands now, the U.S. Department of Health and Human Services ordered 250 million doses of the regular, unadjuvanted vaccine. Of those, only 38 million doses had been delivered as of Nov. 6.

So who are Health and Human Services and the Centers for Disease Control and Prevention blaming for the shortfall? The vaccine manufacturers.

But in reality, the blame is shared, with some of the responsibility indeed falling on vaccine manufacturers, but also on government agencies, and, yes, even on citizens.

Several vaccine makers, such as Novartis (NVS), Sanofi-Aventis (SNY) and GlaxoSmithKline (GSK), indeed said problems with growing the vaccine virus caused low yields in manufacturing the vaccine antigen -- the substance that elicits an immune response when introduced to the body. This is the main reason for their inability to fill the orders as promised. But now, they're vowing to fill the orders by year-end.

Adjuvanted Vaccine's Benefits

Many health experts believe the adjuvanted vaccine -- an adjuvant is a substance added to a vaccine to enhance the immune response to the vaccine -- would vastly improve the nation's current supply of vaccine. "All of us in the vaccine community would welcome an adjuvanted vaccine," said Dr. William Schaffner, chairman of the Department of Preventive Medicine at Vanderbilt University Medical School in Nashville, Ten.

Schaffner added that the adjuvanted vaccine would also boost immunity in patients who are too frail to mount a strong enough response to regular flu vaccines. "It would theoretically achieve both goals of having more vaccine and addressing immuno-compromised and frail patients," he said.

What's more, viruses tend to mutate and the H1N1 virus is a new strain. The use of adjuvant could help protect against future mutations, Schaffner said.

The World Health Organization has recommended using adjuvanted vaccines because of their dose-sparing quality. By not using an adjuvant, the U.S. uses up much more of the global supply of vaccine than needed, Charlotte Schubert wrote in Nature magazine.

U.S. Lags Behind Europe

Europe, Asia and Canada have already embraced adjuvanted vaccines without problems. Glaxo has received orders totaling 440 million doses for its vaccine, mostly for its adjuvanted one. Novartis, too, has begun shipping its adjuvanted vaccine.

An adjuvant would help stretch the U.S. supply of vaccine quite readily. H1N1 unadjuvanted vaccines usually contain 15 micrograms of antigen. Adjuvanted vaccines contain as little as 3.75 micrograms of antigen, such as GSK's vaccine paired with its AS03 adjuvant. AS03 is an oil-in-water emulsion-based adjuvant containing vitamin E.

What do these numbers mean? In theory, the adjuvanted vaccine would yield about four times as many doses than the regular one.

Similarly, Novartis's MF59 is an oil-in-water adjuvant and has been used for 12 years in seasonal influenza vaccines in Europe. Neither of the adjuvants has been approved for use in the U.S., even though both have been widely used and tested.

In fact, neither companies has even applied for approval of the adjuvant, they told DailyFinance. GSK has initiated clinical trials in the U.S., but these will take 12 months before results and the approval process could begin.

Regulators Downplay Need

But if adjuvanted vaccines are used worldwide and could potentially alleviate the shortage, why hasn't the U.S. approved them? Well, Patricia El-Hinnawy, a spokesperson for the U.S. Food and Drug Administration, said that in the past, seasonal influenza vaccine hasn't been paired with an adjuvant in the U.S. As a result, the FDA couldn't approve the adjuvant without the normal regulatory process.

To gain approval of their H1N1 vaccine, manufacturers must use the same "established process" to make the H1N1 vaccine that's been in place for vaccine production for about 50 years. As for the adjuvant, the FDA declined to comment on what they have referred to as "uncertainties related to adjuvant use." These uncertainties have not been detailed.

Health and Human Services did purchase the adjuvants from GSK and Novartis as a contingency plan. The department plans to add them to the existing H1N1 antigen to get more vaccine if that situation ever becomes necessary. In that case, the FDA would the issue an Emergency Use Authorization. But Sarah Alspach, a GSK spokesperson, said the U.S. hasn't asked the company to fill the adjuvant order yet.

For now, the FDA doesn't see the need to use adjuvants, the FDA says. "Because we feel the vaccine supply is sufficient, we're not considering at this point the use of adjuvant," El-Hinnawy said.

The Anti-Vaccine Movement

There may be another reason that adjuvanted vaccines are not going to be showing up in flu clinics anytime soon. Though small, the highly vocal anti-vaccine movement generally protests any potential innovation or improvement. This group usually bases its objection on bogus claims that are immediately refuted by scientific methods.

It's true that because the adjuvant boosts the immune system, it can increase the temporary pain, swelling or fatigue caused by a vaccine. Those side-effects have been a concern of some, even if they are still mild compared to the potential flu complications. Many anti-vaccine groups have therefore targeted adjuvants in their campaigns.

Given the fact that the anti-vaccine lobby is small but organized, it would be tough to introduce innovations such as adjuvants, Schaffner said. Should the FDA authorize the adjuvated vaccine for emergency use, vaccine opponents would likely brand it "experimental," complicating its release.

The anti-vaccine movement, in fact, has been so strong that the FDA found it necessary to write a letter to doctors providing information about the vaccine and dispelling some of the false claims surrounding it.

Better Future Response

Down the road, there may be hope for innovation in vaccines. These medicines used to be a low-profit product. But recently, the vaccines market has become more attractive because of new technologies and a greater need for preventative medicines. Certainly the pandemic showed profits can be made, opening the door to more investments and developments.

Current production methods, though, are still based on 50-year-old methodology of growing the vaccine viruses in chicken eggs. The National Institute of Allergy and Infectious Diseases and vaccine manufacturers are looking into other manufacturing methods, with the end-game being the creation of a universal flu vaccine. In the future, when approved, these could provide faster and better protection in case of another pandemic.

Novartis is already manufacturing a cell-based vaccine that has been approved in Germany and Switzerland. The use of cell-based manufacturing has cut weeks off the time required to begin vaccine production, Novartis told DailyFinance. But this technology, too, is not yet approved in the U.S.

The Swiss company plans to open a cell-based vaccine-manufacturing plant in North Carolina, which could provide 150 million doses of pandemic vaccine within six months of influenza pandemic declaration. But it's unlikely that a cell-based flu vaccine would swiftly win FDA approval.

So far, the response to the pandemic leaves much to be desired. Had this been a more serious disease, how would the U.S., which prides itself for its innovation, react? The hope is, it would use all the latest weapons in its arsenal -- and not just the same old armaments it's been using for the past 50 years.
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