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By Julie Steenhuysen
CHICAGO, Jan 19 (Reuters) - Fighting the flu may soon geteasier.
As early as next year, more modern and more effectivevaccines will hit the market, thanks to investments by the U.S.government and pharmaceutical companies. And even biggerscientific advances are expected in the next decade, including a"universal" flu vaccine given every five to 10 years that wouldfight many strains of a virus, making annual shots all butobsolete.
Experts say it could take eight to 10 more years of testingbefore a universal flu vaccine would be ready. Meanwhile, theyexpect advances that could still incrementally improve the levelof protection vaccines offer and shorten manufacturing times.
In the last 12 months, the U.S. Food and Drug Administrationhas approved two new seasonal flu vaccines that protect againstfour predominant strains of flu instead of three. One is a shotmade by GlaxoSmithKline and the other is a nasal spraymade by AstraZeneca.
In late November, the FDA approved Novartis' newflu vaccine grown in cultures of dog kidney cells instead of theconventional chicken eggs, a faster and more reliablemanufacturing process that could help build stockpiles in theevent of a pandemic.
And this past week, the FDA green-lighted the firstgene-based flu vaccine by Protein Sciences Corp, which usesgenetic engineering to grow portions of the virus in insectcells. "This means there are going to be more manufacturersand more types of vaccine available in future flu seasons," FDACommissioner Dr. Margaret Hamburg said in a teleconference onFriday.
Flu vaccines have not been high-revenue generators for majorpharmaceutical companies compared with big-selling drugs fordiabetes, heart disease, rheumatoid arthritis and cancer.Vaccines are expensive to make, and the flu can mutatesignificantly from season to season. In a mild flu season,companies can be left with millions of unsold doses if the fluseason is mild.
Interest in vaccines spiked after a particularly deadlystrain of bird flu known as H5N1 re-emerged in 2003, raising thethreat of a global pandemic that could kill millions. At thetime, there were just two vaccine manufacturers located on U.S.soil.
A year later, U.S. flu vaccine supplies were devastated by contamination at a plant in Liverpool, England. That helpedunderscore the need for America to have its own manufacturingcapabilities, said Robin Robinson, director of the U.S.Biomedical Advanced Research and Development Authority, orBARDA, a part of the U.S. Department of Health and HumanServices (HHS).
Part of the fear was that in a pandemic, countries might betempted to commandeer all flu vaccines made within theirborders, leaving the U.S. exposed. "We needed to develop newvaccines using modern technologies that would make not only morevaccine available sooner, but also make it more effective,"Robinson said.
A FASTER, SAFER PROCESS
Current flu vaccines are mostly grown in fertilized chickeneggs using a 60-year-old method that requires hundreds ofmillions of eggs. The technique can take up to six months and isan arduous process, prone to manufacturing problems.
First, experts at the World Health Organization and the FDAhave to predict which flu strains will be causing most of theillness in the coming season. Then, they make seed strains ofthe flu from people who are infected, which must then bemanipulated into a form that will grow in live chicken eggs.
At every step there is risk for contamination. In some yearscertain flu strains have refused to grow readily in eggs, andthe end product only protects 50 to 70 percent of people who getit. The vaccine for the current flu season is estimated to havea 62 percent effectiveness rate.
With newer methods, companies can skip the egg portion ofthe process altogether.
In 2006, HHS provided more than $1 billion in contracts tosix manufacturers to develop cell-based flu vaccine technologyin the United States. Although its use in flu vaccines is new,cell-based vaccine technology has been around for years,offering a faster, more reliable alternative to egg culture.
In 2009, spurred by difficulties in growing vaccine for theH1N1 swine flu pandemic, HHS provided Novartis with nearly $500million to build the first U.S. facility capable of producingcell-based vaccine for seasonal and pandemic flu in the UnitedStates. Novartis picked up the rest of the estimated $1 billionprice tag.
The following year, Novartis opened a plant in HollySprings, North Carolina, which was approved to make pandemicdoses of H5N1 bird flu vaccine in late 2011. Last November,Novartis' Flucelvax became the first cell-based flu vaccine towin U.S. regulatory approval.
Novartis made a limited supply of the new vaccine availablefor this flu season, and more will be sold once the plant islicensed for seasonal flu production.
Baxter International Inc, one of the initial sixcompanies to win an HHS grant, is almost ready to apply forapproval in the United States for its cell-based flu vaccinePreflucel, which is already approved in 13 European countries.
TINKERING WITH GENES
The United States has also backed new approaches that usegenes or proteins to make vaccine.
In 2009, HHS' five-year, $147 million investment helped bailout then-struggling Protein Sciences, and the tiny biotech hasnow produced the first gene-based vaccine to win FDA approval.
"The new technology offers the potential for faster start-upof the vaccine manufacturing process in the event of a pandemic,because it is not dependent on an egg supply or on availabilityof the influenza virus," Dr. Karen Midthun, director of theFDA's Center for Biologics Evaluation and Research, said inannouncing the approval on Wednesday.
Protein Sciences says its vaccine, called FluBlok, has threetimes the active ingredient traditional vaccines have andcontains no preservatives, which some people object to. It canalso sidestep some of the risk of infection associated withvaccines grown in eggs.
Instead of using the whole virus, Protein Sciences makes itsvaccine using a single flu gene known to evoke a strong immuneresponse. The company places this into a harmless insect viruscalled baculovirus. The virus grows inside insect cells, whichare then purified to become a basic part of a human vaccine.
Two other genetically engineered flu vaccines are also underdevelopment. One by Novavax of Rockville, Maryland,uses bits of genetic material grown in caterpillar cells called"virus-like particles" that mimic a flu virus.
The other HHS partner is VaxInnate Corp, a private companyin Cranbury, New Jersey, run by Wayne Pisano, former chief ofSanofi's vaccine operations in Swift Water,Pennsylvania.
In 2011, HHS awarded VaxInnate a five-year, $196 milliongrant to make a vaccine that combines a bacterial protein calledflagellin, a potent stimulator of the immune system, with a verysmall portion of flu virus called hemagluttinin, the outsidepart of the flu protein that gives flu viruses the "H" in theirnames.
VaxInnate's flu vaccine is in mid-stage clinical trials. On Wednesday the company signed a license agreement with EmergentBioSolutions Inc, which also has a contract with HHS.
Robinson expects both the Novavax and VaxInnate vaccines tobe available in the later part of the decade.
LESS FREQUENT, MORE EFFECTIVE SHOTS
HHS is now focusing on a universal flu vaccine that could begiven every five to 10 years, much like a tetanus shot, andprotect against most types of flu, including seasonal varietiesand the highly mutated kinds that cause pandemics.
Only about a third of the U.S. population gets inoculatedagainst the flu, but a universal flu vaccine could vastlyincrease acceptance. Although several teams have tried andfailed, scientists at the National Institute of Allergy andInfectious Disease and others are making good progress,according to Dr. Anthony Fauci, director of the NationalInstitute of Allergy and Infectious Disease, a part of theNational Institutes of Health.
Work by Fauci and Dr. Gary Nabel, former head of NIH'sVaccine Research Center who just joined Sanofi as chief scienceofficer, showed that a portion of the flu virus that is usuallyhidden from the immune system may be the key.
Fauci describes the hemagluttinin part of the flu virus asbulb-shaped with a stem on one end, sort of like a dandelionthat has gone to seed or a lollipop on a stick.
Most vaccines target proteins on the bulb portion of thevirus, which mutates from year to year, but Fauci says the stemcontains proteins that don't change much from virus to virus.
The problem is that when the flu virus is presented to thebody, these stem proteins are structurally hidden from theimmune system. A genetically engineered vaccine could overcomethat by only presenting these stem proteins to the immunesystem.
Phase 1 studies have already begun in people, testing forsafety and whether the vaccine can prod the immune system intomaking an appropriate response.
Robinson said the science has reached a stage where BARDA isgetting involved.
Both HHS and NIH are working with a team led by Peter Palesefrom the Mount Sinai School of Medicine in New York. Robinsonsaid BARDA will be handling the manufacturing of the vaccinealong with colleagues at Novartis, and the clinical trial willbe done by NIH.
"It's a good hypothesis that we can test and hopefully itwill work. We're keeping our fingers crossed," Robinson said. (Writing and reporting by Julie Steenhuysen with additionalreporting by Bill Berkrot in New York; Editing by Jilian Mincerand Prudence Crowther)
