National Institute of Allergy and Infectious Diseases

A new flu vaccine is made out of self-assembling nanoparticles. This images shows what the particle looks like - to the immune system, it looks like a flu virus.

Researchers have developed a “stripped down” synthetic flu vaccine that they believe will not only work better than current vaccines, but might last longer, too -- saving people from having to get a fresh flu shot every year.

They say it’s the first step toward a new generation of influenza vaccines, designed entirely in the lab, using nanoparticles instead of the decades-old approach that uses chicken eggs. The nanoparticles assemble themselves into an imposter of the flu virus -- one that seems to excite the immune system far more than the real thing.

“This is, I believe, an important advance,” says Dr. Tony Fauci, head of the National Institute of Allergy and Infectious Diseases, where the research was done.

Current flu vaccines are clunky at best. Most are still grown in eggs, an uncertain technology that takes months. Entire factories full of vaccine can be shut down because of contamination. Researchers have figured out how to make synthetic versions of the flu virus to use as a basis for the vaccine, but many still use real viruses, either killed or weakened so they don’t make people sick.

And it’s never certain from one year to the next how well the vaccine will work. No one is precisely sure why, but the virus mutates every year, and a variety of strains circulate at any given time. The result is that some years the vaccine protects people well, and in others, it doesn’t.

For instance, this past season’s influenza vaccine reduced the chances of illness by just 9 percent in people older than 65, the Centers for Disease Control and Prevention says, and reduced illness for the population as a whole by 56 percent.

And then every few years, a new strain pops up to infect people. Health officials are currently keeping a wary eye on two strains of bird flu, H5N1 and H7N9, either of which could mutate just a bit more to cause a pandemic.

The new vaccine uses a key part of the flu virus, called hemagglutinin, which gives flu the “H” in its name.  Dr. Gary Nabel, who was at NIAID at the time, fused a bit of hemagglutinin to a piece of a compound called ferritin. Ferritin naturally makes itself into little nanoparticles, and the result was a nano-sized spiky ball that looked a lot like a natural bit of hemagglutinin.

Nabel says it’s a stripped-down version of flu virus that the immune system recognizes even better than it does real flu. Tests on animals showed the nanoparticles caused the body to produce 10 times as many virus-fighting antibodies as the current seasonal flu vaccine, Nabel’s team reports in the journal Nature.

“They look like flu. They react with antibodies like flu,” Nabel, who now works for vaccine maker Sanofi, said in a telephone interview.

The vaccine protected ferrets against H1N1 flu viruses, an H3 flu virus and an influenza B virus, too. Ferrets are the animals that react most like humans to flu.

Now researchers are working to make a version that can be tested in people.

Nabel thinks the vaccine will provide broader immunity than current vaccines, as well as a stronger immune response. But humans have unique immune systems and it’s not yet clear how it will work in people.

It may also speed up the convoluted process for making vaccines, which starts with growing the virus in the lab, something that can take months. “We don’t need the virus to replicate. We just put the gene into a cell and make the particle. It is rather an amazing process,” Nabel says.

“In theory it could be very fast.” If it takes three months now to make a “seed” virus for a vaccine, the new process would only take a week or two, he estimates.

It took months to make and roll out vaccine against H1N1 swine flu when it first broke out in 2009 and thousands of people died during the delay. CDC doesn’t count how many adults die from flu each year, because it’s so variable -- anywhere from 4,000 to 49,000 a year.

The new technology might not just work against flu. “This is a platform that could be used for other viruses,” Nabel said. That could include the AIDS virus or herpes, or even coronaviruses like the new MERS virus that has killed more than 20 people in Saudi Arabia and other middle east countries.

Fauci said in theory, a vaccine made from this new technology could last longer than the current seasonal flu vaccine. “To me, this is an important step toward the development of a universal flu vaccine,” Fauci said. “The definition of a universal flu vaccine is it covers wide range (of virus strains) and you wouldn’t necessarily need to get a new one each year.”

Dr. John Treanor, a flu vaccine researcher at the University of Rochester Medical Center, said the approach resembled some newer-generation vaccines that use synthetic technology and that have been shown to work in people.  “It certainly is a very technically advanced approach,” said Treanor, who was not involved in the research.

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Centers for Disease Control and Prevention

A CDC scientist harvests H7N9 virus that has been grown for sharing with partner laboratories for research purposes.

More than 50 travelers just back in the United States from China who had flu-like symptoms have been tested for the H7N9 bird flu virus, federal health officials say. So far, none has tested positive.

But the fact that they’re being tested at all shows just how worried the U.S. government is about this new strain of bird flu, which threatens at the same time as a still-mysterious coronavirus from the Middle East. The test kits had to be specially made up and distributed under an emergency provision.

“While no cases of H7N9 have been detected at this time in the U.S., 54 people with flu-like symptoms after travel to China have been tested. All have 54 tested negative for H7N9; while six tested positive for seasonal influenza A, and three tested positive for seasonal influenza B,” the Centers for Disease Control and Prevention says in its latest update on the virus.

Emergency operations centers are running 24/7, keeping an eye on both situations. While it's not unusual for the centers to be operating around the clock, it is rare to have two pandemic threats at once to plan for, says Edward Gabriel, who heads preparedness and response issues at the health and Human Services Department. 

"We want the latest and best information that we can get," Gabriel told NBC News. "We also need to look and see where it is moving to. To try to isolate its motion is a pretty significant thing."

If either virus turns into a form that spreads easily from person to person, a pandemic could follow within weeks. Both seem especially deadly in their current form: H7N9 seems to have about a 20 percent fatality rate, while the new coronavirus appears to have killed more than half its victims.

“In the case of the two latest threats — the H7N9 influenza virus and the new coronavirus — the number of infected people is small, and the infections are occurring thousands of miles away from the United States. Yet we should be seriously concerned about both,” Mike Osterholm, an infectious disease expert at the University of Minnesota, wrote in the New York Times on Friday.

“Our public health tools to fight these viruses are limited. We have no vaccines or effective drugs readily available to stop or treat the new coronavirus in the Middle East,” Osterholm adds. 

CDC

Influenza A H7N9 as viewed through an electron microscope. Both filaments and spheres are observed in this photo.

The H7N9 flu can spread silently, as people transmit influenza before they’re sick themselves. If the flu did mutate into a pandemic form, it would probably take at least six months to make enough vaccines to protect large numbers of people.

“It may take longer than it takes the virus to spread,” says Dr. John Treanor, a flu vaccine expert at the University of Rochester Medical Center. “The technology that we have today is such that the bulk of the pandemic disease may have already taken place before a vaccine is in place and can be used,” he added.

“The virus can spread very, very quickly. You are in a race against time.”

That happened in 2009, when the new strain of H1N1 swine flu broke out to cause the first pandemic of a new flu in 40 years. Companies raced to make vaccine but it was months before it was ready.

There are drugs to fight flu – a pill called Tamiflu and an inhaled powder called Relenza. Neither is a cure, however, and both need to be given very quickly to do much good at all.

Right now, H7N9 seems mostly confined to China and the spread has slowed. The World Health Organization reports 32 people have died out of 131 lab-confirmed cases.

“The drop-off in newly reported H7N9 cases in China may be the result of containment measures reportedly taken by Chinese authorities, including closing live bird markets, a venue where the risk of exposure to bird flu viruses can be high," the CDC says. “However it may also be a result of changing seasons, or a combination of both.”

Researchers in Hong Kong did a computer analysis of the outbreak and estimate that at least 200-500 more people have likely been infected with H7N9. The virus seems to cause serious illness mostly in people over 65 – doctors are not sure why yet.

“We estimated that risk of serious illness after infection is 5.1 times higher in persons 65 years and older versus younger ages,” Ben Cowling and colleagues at Hong Kong University wrote in the journal Eurosurveillance.

The evidence suggests that most of the patients got infected directly by birds, probably in poultry markets. So Cowling’s team took all the data and estimated how many younger people were likely to have been infected without knowing they had H7N9. "Our results suggest that many unidentified mild influenza A(H7N9) infections may have occurred, with a lower bound of 210–550 infections to date," they wrote. This would mean the virus isn’t that widespread, but which also confirms its high fatality rate. 

The coronavirus, which some are dubbing Middle East Respiratory Syndrome Coronavirus, or MERS, is a little different story. WHO says 33 infections have been reported, with 18 deaths. Experts are watching cases in France, where one patient who traveled from Dubai was confirmed to have the virus. 

A man who shared a hospital room with the 65-year-old man also has the virus, French officials said Sunday -- something that shows the virus and and does spread in hospitals. 

Officials were relieved that three health care workers who cared for the 65-year-old patient and who got sick have tested negative for the virus.

Also Sunday, WHO Assistant Director-General Keiji Fukuda could probably be passed between people in close contact, but there was no evidence of sustained "generalized transmission in communities."

Some reports suggest an outbreak in Saudi Arabia also affected people in the same hospital.

This worries Dr. Eric Toner of the Center for Health Security at the University of Pittsburgh Medical Center. SARS – severe acute respiratory syndrome – also spread mostly in hospitals. SARS spread to 29 countries in 2003, killing 775 people and making 8,000 sick before it was stopped.

“These cases, whether confirmed or not, should be a wake-up call,” Toner writes in his blog.

The good news is that SARS was stopped using good hospital hygiene. Face masks, gloves and careful disinfection prevented its spread. And SARS only spread once people were noticeably ill, unlike flu, which people can spread before they feel sick and after they feel better.

The bad news is that hospitals may have forgotten this lesson. “SARS was stopped by healthcare workers being aware of the disease, having a high index of suspicion of anyone with fever and respiratory symptoms who had recently been in an affected region, and quickly implementing infection control measures with any suspect case,” Toner says.

“Until now, all cases of MERS originated in the Middle East, but as the confirmed French case demonstrates, the virus is only a plane ride away from other parts of the world. In the 10 years since the SARS outbreak, many hospitals have become lax in their attention to respiratory precautions.”

Gabriel says he’s working to make sure this isn’t the case with U.S. hospitals. “Hygiene practices are now better than they ever have been,” Gabriel said. “We send out reminders daily.”

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This story was originally published on Sun May 12, 2013 9:33 AM EDT

A drug that flopped in tests to treat sepsis may offer a new way to treat influenza, researchers reported on Wednesday.

If it works in people, it might provide a new defense against emerging new viruses such as the H7N9 bird flu virus circulating in China, other experts said.

Tests in rodents show the drug appears to stop the immune system overreaction that so often kills people infected with influenza and other viruses, the researchers report in the journal Nature. And because it acts on the patient, and not on the virus, it may be immune to the mutations that make so many viruses resistant to drugs.

“We hope it’s a new flu drug,” says Stefanie Vogel, a researcher at the University of Maryland school of medicine who led the research. “This is the first drug to come along for flu where you are not focusing on the virus… What was exciting about our paper is we showed that even starting the drug as late as six days after the infection gave us significant improval in the life of the mice.”

Most strains of influenza have already evolved resistance to the first two flu drugs – amantadine and rimantadine. There are two newer drugs on the market – a pill called Tamiflu and an inhaled powder called Relenza. But there are strains of flu that already elude the effects of Tamiflu.

There’s a third drug, called peramivir, but it’s not widely used. And viruses can evolve resistance to that drug, too.  It’s the same problem that plagues antibiotics, the drugs used to fight bacterial infections. So-called “superbugs” have evolved that can resist the effects of many different drugs.

Health experts are keen for an antiviral drug that will work no matter how the virus mutates. One way to do this is to affect the immune response of the patient.

The new drug, called Eritoran, was originally developed by the Japanese drug company Eisai Co. to fight sepsis. Doctors believe sepsis is a form of immune system overreaction that can kill after an infection or injury.  Eritoran was shown to be safe in people, but it didn’t work well against sepsis.

Vogel’s team had noticed that the drug worked against a particular part of immune system cells called TLR4. They also knew that lab mice genetically engineered to lack TLR4 seemed particularly immune to flu. Could blocking TLR4 make people immune to flu’s effects on the immune system, too, they asked?

It did. Tests in a second rodent called a cotton rat showed this, too. Vogel’s team wants to do further tests but they hope this may provide a new and better way to treat influenza.

Flu usually doesn’t kill people, of course. It just causes unpleasant symptoms such as fever, cough and muscle aches. But it can cause pneumonia and in some people, including perfectly healthy young people, it can cause an immune system overreaction called a cytokine storm. Vogel calls it a cytokine avalanche.

“You need a certain amount of imflammation to be able to fight off the attacking agent,” Vogel said. “But when the inflammation spins out of control, then you end up hurting yourself.”

Joan Nichols, a flu expert at the University of Texas Medical Branch in Galveston, says the study shows Eritoran has a lot of potential. “One of the things we need is a broad-spectrum influenza drug,” she said in telephone interview.

One of the weaknesses of Tamiflu is that it must be taken within a day or two of symptoms showing up to be effective. The new drug might work after people become seriously ill with flu. “This drug could be used to treat people who are already symptomatic,” Nichols said. “You might not see as many deaths.”

A new strain of bird flu called H7N9 avian influenza has already infected more than 120 people in China and killed 27 of them. Tamiflu seems to help, but if the new virus spread and mutated into a form that infected people more easily, it could cause a pandemic. It would take months to make a vaccine, and drugs would be the best defense until one was ready.

“This would be useful in outbreaks like the H7N9,” Nichols said. “No matter what strain of influenza you see emerge, we have got a drug that could buy us some time.”

The approach might also be useful against other viruses that also cause an immune system overreaction, such as severe acute respiratory syndrome (SARS), says John Teijaro, senior research associate at The Scripps Research Institute who specializes in studying these cytokine storms. “Aberrant immune responses have been implicated in the pathogenesis of acute respiratory viral infections including influenza, SARS and hantavirus,” he said in a statement.

SARS, a so-called coronavirus, swept around the world in 2003, infecting around 8,000 people and killing 800 before it was stopped. Health experts are keeping a wary eye on a new type of coronavirus first seen in the Middle East that has killed at least 16 people.

And, said Nichols, the drug has already gone through clinical trials to show it’s safe in people. “Say we needed it tomorrow. They could probably push this,” she said.

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Wang Zhao / AFP - Getty Images

A new strain of bird flu identified in China "is one of the most lethal influenza viruses we have seen so far," Dr. Keiji Fukuda, the World Health Organization (WHO)'s Assistant Director-General for Health Security, tells journalists at a press conference in Beijing on Wednesday.

BEIJING – A new type of bird flu that has killed 22 people in China since March is one of the most deadly strains of influenza known, international health experts said on Wednesday. 

"This is one of the most lethal influenza viruses we have seen so far," said Dr. Keiji Fukuda, the World Health Organization (WHO)’s Assistant Director-General for Health Security. "We are at the beginning of our understanding of this virus."

The H7N9 strain appears to spread more easily to humans than SARS, a different virus that started killing people in Asia a decade ago, experts said. Severe acute respiratory syndrome killed around 800 people globally in 2003 before it was stopped.

"This is an unusually dangerous virus for humans," added Fukuda, who was speaking in Beijing alongside leading flu experts from around the world.  

The delegation from United States, Europe, Hong Kong and Australia, as well as China, have just concluded a week-long investigation that took them to affected areas in Shanghai and Beijing.

Little is known
The group of experts made an impressive display of international cooperation, but at the same time admitted just how little is known about the virus that has infected 108 people since March.

"We are at the very early stages of this investigation," said Dr. Nancy Cox, who heads Influenza Division at the Center for Disease Control and Prevention in Atlanta. "There's a lot to be learned.”

Most of the cases so far have been found in eastern China, around the Yangtze River delta, but in recent days there have been cases in central and northern China, including the capital. Most have been what Fukuda called "sporadic cases."  

He said a few family clusters have been found, which could be the result of exposure to the same source of virus, or limited person-to-person transmission.

But he said: "'Evidence so far is not sufficient to conclude there is person-to-person transmission. Moreover, no sustained person-to-person transmission has been found.”

The experts concluded that live poultry markets were the most likely source of infection.

The experts praised the swift action of Chinese authorities in closing live poultry markets, and said it was "encouraging" that there have been no new cases in Shanghai since its markets were shuttered.

And they called for continued international cooperation against a virus that doesn't recognize borders. 

"The risks of an outbreak situation are shared in a globalized world, where we are all interconnected," said Fukuda.

Legacy of distrust
All of those who spoke today went out of their way to praise the response and of the Chinese authorities and their openness and transparency. There is enormous sensitivity to any suggestion that their presence in China implies any criticism of local efforts.

China still lives in the shadow of the SARS pandemic, which began here a decade ago and killed hundreds worldwide, including in the U.S. It was made worse by an initial cover-up by the Chinese authorities.

"The response reflects earlier and strong investments in health and preparedness made by China," said Fukuda.

SARS also left a legacy of distrust, which was on display earlier in the week in Shanghai, when a press conference by the local government and WHO was gatecrashed by the daughter of a couple infected with H7N9. The 26-year-old demanded information about her quarantined father; her mother had died.

"The hospitals and medical staff appear friendly to members of the media like you but have responded in a lukewarm manner to inquiries from family members like me," she told the South China Morning Post. She was taken away by officials.

The experts said that in the absence of so much basic information about the extent of the public health risk it was critical to maintain a high level of awareness. They also noted that the weather is warming up in China, which might provide a bit of a respite and buy them some important time, since H7N9 -- in common with other influenza -- spreads less easily in the spring and summer.

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This story was originally published on Wed Apr 24, 2013 6:19 AM EDT

A new genetic analysis shows the H7N9 bird flu in China may have been spreading quietly for weeks or months in domestic animals. But it mutates once it infects a person, giving birth to new viruses that feel more at home inside the human body.

Doctors have diagnosed 102 people in China with H7N9 and 20 people have died of it, according to the Chinese news agency Xinhua. So far they are all in eastern China, with one case in Beijing, but China has welcomed World Health Organization experts to help figure out where the virus has come from, how far it has spread, and how big a threat it really is.

The new Dutch study suggests the virus has been spreading unnoticed among domestic animals in China, and that a certain mutation may make it deadlier in people. In 2003, a strain of flu called H7N7 spread to 255 poultry farms in the Netherlands, forcing the slaughter of 30 million chickens. About 450 people got mild illness and one veterinarian died from an H7N7 infection.

Researchers compared the genetic sequences of viruses from that outbreak to the new H7N9 virus. It has enough mutations to suggest it's been changing over time --although it's impossible to put a precise time frame on it. Influenza viruses are prone to making mistakes as they replicate, giving rise to all sorts of different mutations, often within the same person or animal.

Virus taken from the vet who died in 2003 had a genetic mutation that made the virus particularly virulent. It probably evolved inside the patient’s body, Marcel Jonges of the National Institute for Public Health and the Environment and colleagues say. “Remarkably,” they wrote in the journal Eurosurveillance, four samples taken from Chinese patients who died have the same mutation.

The gene sequences also suggest the virus has been quietly infecting animals, they added. “The data are suggestive of (silent) spread and adaptation in domestic animals before the novel A(H7N9) virus was identified in humans,” they wrote. And, they noted, in the Dutch H7N7 outbreak, many of the human patients had eye infections known as conjunctivitis.

Chinese health experts are testing healthy people who have been in contact with H7N9 patients. They haven’t found much evidence that people have been infected and spread the infection without becoming sick themselves, but it may be important to check their eyes, the researchers suggest. Flu viruses can infect the eyes and the H7 strains may be easier to find there, they said.

The quiet spread has been making H7N9 hard to track. Avian influenza viruses can be highly pathogenic, or low pathogenic. The other bird flu virus out there that worries health experts, H5N1, is a highly pathogenic virus. It’s easy to track in chickens, because it kills off flocks en masse, although it doesn’t make most ducks sick. Officials can cull flocks as soon as it shows up.

But H7N9 doesn’t seem to make birds ill, so it’s hard to tell what species are infected and how widespread it is. There’s also not a good, easy-to-use test for it yet.

“It is a sneaky virus,” says Hon Ip, who’s been tracking bird flu viruses for the U.S. Geological Survey’s National Wildlife Health Center in Madison, Wis. He’s seen flu viruses mix more than once to infect new species, such as when a bird flu virus called H3N8 infected and killed seals off the New England coast in 2011.

“This is exactly similar to the situation currently with the H7N9 virus, which is also an avian influenza virus that causes disease in a mammalian species, namely people,” Ip said in a telephone interview.

China’s State Forestry Administration said its checks have so far found no H7N9 virus in more than 800 wild birds sampled in five cities and provinces where human infections have been reported.

Last week, a study published in the New England Journal of Medicine suggested several different bird flu viruses mixed genes to give rise to the new H7N9 strain. Flu viruses often swap their genetic material in this way -- the H1N1 virus that caused the 2009 swine flu pandemic was a mixture of bird, pig and human viruses.

Rongbao Gao of the the Chinese Center for Disease Control and Prevention in Beijing and colleagues said their team’s genetic analysis traced the virus to a colorful and common species of finch called a brambling. It mixed with viruses from two other bird types, including, evidently a duck from the Yangtze River Delta and a wild bird from Korea, to make the new H7N9 strain.

So how are people getting infected? In the case of H5N1, almost all the 600-odd people infected since 2003 have had direct contact with poultry. But many of the Chinese H7N9 patients say they haven’t.

“One possible explanation for this could simply be recall bias -- people often forget what they have done,” says Dr. Eric Toner of the Center for Biosecurity at the University of Pittsburgh Medical Center.

“Another explanation could be that human-to-human spread of the disease is occurring but has not yet been detected, even though close observation of more than 1,000 known contacts of confirmed cases has yet to show evidence of transmission,” Toner adds in his blog.

It could be that restaurants are spreading the virus if they slaughter birds on site, Toner says, or other animals could be carrying it, Toner says. Pigs often give new flu viruses to people but Chinese authorities say they haven’t found H7N9 in pigs so far.

There’s no evidence anyone outside China has been infected. But U.S. officials warned doctors this week to keep an eye out for it.

“This is a 'novel' (non-human) virus and therefore has the potential to cause a pandemic if it were to change to become easily and sustainably spread from person-to-person,” the Centers for Disease Control and Prevention said in a statement.

“So far, this virus has not been determined to have that capability. However, influenza viruses constantly change and it’s possible that this virus could gain that ability,” it added.

The CDC briefed infectious disease experts on what to do. Anyone who has severe symptoms and has recently traveled to China should be treated immediately with antiviral drugs – either Tamiflu or Relenza, the CDC says.

“Given the anticipated lack of preexisting immunity to H7N9 viruses, the potential for rapid progression, severe disease, and fatal outcomes with H7N9 infection, and low adverse event profile of neuraminidase inhibitors, treatment with oseltamivir or inhaled zanamivir should be initiated when confirmed cases, probable cases, or H7N9 cases under investigation are recognized, even if more than 48 hours from illness onset and even for apparently uncomplicated illness,” the CDC advises.

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• Don't panic yet, CDC says

Less than two weeks after Chinese officials released the genetic sequence of a new type of bird flu, U.S. vaccine experts are well on the way to making a vaccine to protect people against it.

There’s no evidence the H7N9 virus would ever threaten the U.S. It’s been diagnosed in fewer than three dozen people, all restricted to eastern China. People don’t appear to be infecting one another, at least not in large numbers.

But it’s already killed nine of them. Scientists said Wednesday that the virus seems to have been the result of genetic reassortment of wild birds from east Asia and chickens from east China, Xinhua, the official Chinese news agency reported. Still, it doesn’t seem to be making birds sick -- which means authorities don’t have tell-tale die-offs of poultry to warn them when it’s circulating.

And it takes months to make influenza vaccines, so every day may count.

“It puts flu back on people’s minds,” said Dr. Amesh Adalja, an emergency physician at the Center for Biosecurity at the University of Pittsburgh Medical Center.

It’s just the kind of situation that flu experts have been been rehearsing for. They hope to do better than in 2009, when it took until October to deliver the first vaccines against the pandemic of H1N1 swine flu.

“The virus was identified in March,” notes flu expert Dr. Arnold Monto of the University of Michigan. Six long months ticked by with the virus spreading and no vaccine against it.

The U.S. government was battered by criticism from confused Americans who tried hard to get flu vaccine but couldn’t, and then gave up trying just about the time that vaccines started being produced and delivered in quantity.

Vaccine makers ended up throwing away about 70 million doses. “We can do it faster,” Monto said.

Two seasonal flu vaccines that use new technology approved within the past six months should help speed up the process. That same techonology can be used to make other vaccines, including one to protect against H7N9. And Dr. Robin Robinson of the Biomedical Advanced Research and Development Authority (BARDA), part of the Health and Human Services Department, says H7N9 is giving his department the chance for what he hopes will be a dry run.

“I think we are in a much better place than we were before the pandemic of 2009,” Robinson told NBC News. “We have some ongoing initiatives that are starting to provide real results.”

Most flu vaccines are made using technology that dates back to the 1940s. Doctors isolate the virus from a patient, combine it with another virus used to make the a “seed” for the vaccine, grow it in specially fertilized chicken eggs, strain it out and purify it – a process that takes months and that is fraught with dangers, not the least of which is contamination of the eggs.

Newer technology dumps the eggs. One new vaccine is grown in insect cells, and another is grown in cells taken from a single cocker spaniel’s kidney decades ago. That speeds things up a bit. And now scientists can make vaccine based on the genetic sequence, because they can make artificial genes in the lab.

So they can go straight from a genetic sequence published online to starting to make a vaccine. This method, called recombinant technology, shaves a few weeks off the process. Last summer, when a new strain of swine flu called H3N2v infected about 300 people and killed one, mostly via state fairs, drug maker Novartis and experts at the J. Craig Venter Institute in California made a seed virus for the vaccine in a week, Robinson says.

“Now with the H7N9 outbreak in China, the nucleotide (genetic) sequence was available Saturday, March 30,” Robinson said. Scientists at Novartis, with the federal government and the Venter Institute synthesized the necessary genes by the following Tuesday. By Wednesday, they had inserted the artificial gene sequences into dog cells and were growing new virus.

“Now we are characterizing that … virus to see if we have the right seed strains,” Robinson said. If they are, they’ll be tested and prepared to make a vaccine.

“We have been able to shave weeks off the method,” Robinson said.

When samples of the actual virus are released later this week, vaccine makers using old-fashioned methods will go to work on those, Robinson added.

“We have talked to all the manufacturers that make egg- based, cell-based and recombinant-based vaccines to ask what their manufacturing capabilities are,” Robinson said. HHS will know by the end of this week how much vaccine the companies can make and when they could have it ready, he says.

In any pandemic, the goal is to vaccinate every American. What's not clear is how many doses would be needed for protection and whether manufacturers could create enough in time.

The United States has invested heavily in vaccine technology since about 2004, when it became clear that H5N1 bird flu was a threat. So far, H5N1 has been an expensive nuisance, forcing the culling of hundreds of millions of birds, and killing 60 percent of the 600 or so human victims who have been infected.

But it could mutate into a form that passes easily from human to human. So could H7N9. Or another type of flu could emerge. Seasonal flu vaccines provide no protection at all against these new strains.

Some people have criticized the U.S. government’s reliance on commercial flu vaccines. It’s spent $147 million in five years to help companies that were struggling to develop new vaccine technology.

Seven companies make flu vaccines for the U.S. market, and the CDC and HHS are heavily invested in encouraging people to get vaccinated each year, not only to protect themselves from flu, but to keep a market incentive for companies to make flu vaccine.

But Monto says it’s the only way. “If the companies were not involved in producing a vaccine and taking risks each year, we wouldn’t have vaccines,” he says. And seasonal flu is nothing to sneeze at -- killing upwards of 40,000 people in a bad year.

Robinson says these preparedness efforts have been spared so far from budget cuts hitting other areas of government.

“We plan for these kinds of things to happen,” he said. “So far we are OK in developing the actual vaccine candidate. Where we get into trouble and will have to ask Congress for more money is if we have to have a large vaccine campaign like we had in 2009.”

Related:

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Brian Snyder/Reuters

Chihn Ha, 8, gets an influenza vaccine injection from nurse Nho Nguyen, right, during a flu shot clinic at Dorchester House, a health care clinic, in Boston, Mass., in January 2013.

The longer-than-average flu season finally appears to be ending, federal officials said on Friday, but it’s not quite done yet. Only six states, mostly in the Northeast, are now reporting widespread influenza.

The deaths of another five children were reported this past week, bringing the total for the season to 110, the Centers for Disease Control and Prevention reports. That’s just around the unfortunate average for influenza in any given year, the CDC says, although it varies a lot.

The viruses circulating this year were especially hard on people 65 and older and CDC is still trying to work out just how well vaccines may or may not have protected people, especially the elderly, against serious illness and death from flu. So many adults die of flu every year that the CDC can’t keep a precise count, but estimates that it ranges from a low of 3,000 to as many as 49,000.

This year was a “moderately severe” flu year, CDC says in a review of the 2012-2013 influenza season.

“This season, influenza activity started about 4 weeks early and was intense. Influenza-like-illness rose quickly to well above the baseline of expected activity and remained elevated for 15 consecutive weeks, making this season slightly longer than average,” the agency says in a statement.

“Flu-associated hospitalizations began to rise in mid-December with sharp increases seen among people 65 years and older.”

Half of the patients sick enough to be hospitalized with flu were 65 or older, CDC said. “While hospitalization rates have leveled off, this is the highest proportion of persons 65 and older hospitalized for flu that has been measured since this kind of record-keeping began during the 2005-2006 season,” it said.

Sadly, a few were children, and most had not been vaccinated, CDC said. “CDC reported an additional five pediatric deaths this week for a total of 110 to date for the 2012-2013 season. The number of pediatric deaths is likely to climb further as additional deaths are reported,” CDC said. Reports of deaths can take weeks to collate -- some of the five deaths reported this week dated back to December.

Experts have done a batch of studies to see how well the flu vaccine worked this year. That varies from year to year and scientists still are not sure why flu vaccination protects more strongly in some years than in others.

Flu vaccines have to be formulated freshly each year to protect against the most common circulating strains of virus. This year’s vaccine protected against three strains – one called H3N2, one called H1N1 – a descendant of the H1N1 “swine flu” that emerged in 2009 – and one influenza B strain.

Next year’s vaccines are just being formulated now, based on what’s circulating, and some will protect against four strains of flu.

“February results showed the 2012-2013 flu vaccine reduced the risk of flu-associated medical visits from influenza A (H3N2) viruses by one half and from influenza B by two-thirds for most of the population,” the CDC said.

 “This means that vaccinated people reduced their risk of having to go to the doctor for influenza by more than half, thus providing significant benefit to the person getting vaccinated and to public health in general.”

But it only prevented the risk of severe disease by 27 percent among people 65 and older this year. “It’s possible that some people 65 and older did not mount a good immune response to H3N2 from vaccination,” CDC said.

Related:

• Flu kills 105 kids; most not vaccinated
• Why it's so hard to get the flu vaccine supply right
• Flu spreads to all 50 states

Hotli Simanjuntak / EPA file

A strain of H5N1 virus is believed to have caused the deaths among poultry in Jakarta last fall. Here, traders sell chickens in the Keutapang market, Aceh, Sumatra, Indonesia, on Dec. 12, 2012. Researchers announced Wednesday they will resume controversial research on how H5N1 can transmit through the air.

Scientists said Wednesday they are re-starting some of the controversial research in which they managed to make H5N1 bird flu viruses transmit though the air -- but not in the U.S., where safety concerns haven't been fully addressed. They say they need to understand this in case it starts happening in nature, causing a pandemic.

Since 2003 H5N1 bird flu has infected 610 people globally and killed 360 of them, according to the World Health Organization. While this might not sound alarming, flu experts say it could mutate at any time into a form that passes easily from one person to another, causing a deadly pandemic. But their studied worried a board of U.S. government advisers, which asked them to hold up. They have done so for a year now.

“The risk exists in nature already, and not doing the research is really putting us in danger,” Dr. Yoshihiro Kawaoka of University of Wisconsin-Madison, one of the top influenza researchers in the world, told reporters in a telephone briefing.

Kawaoka was among 40 flu researchers who signed a letter published jointly in the journals Nature and Science on Wednesday, saying they were ready to start their work again.

The 40 scientists have been working for years to figure out just which mutations would give H5N1 the ability to spread easily from one person to another, while also staying deadly.

They mostly work with ferrets, which get infected with flu in a way very similar to how people get infected.

In one of the studies that caused concern, researchers created mutant versions of H5N1 that became airborne, spreading from one ferret to another without any physical contact.

Last December a committee called the National Science Advisory Board for Biosecurity asked two teams of researchers to hold off on publishing their findings. The U.S. government also asked all flu researchers to agree to a moratorium on genetically changing flu viruses until ground rules could be agreed on. The worry was that the virus could escape and accidentally cause a pandemic or, worse, that terrorists could somehow get hold of the work and use it to make a biological weapon.

The researchers say they’ve addressed the concerns in several countries, including Canada and the Netherlands. “Scientists should never conduct this type of research without the appropriate facilities, oversight, and all necessary approvals,” they wrote in their letter.

“The USA is still under final consideration for biosecurity,” said  Dr. Ron Fouchier, who works at Erasmus University in Rotterdam, Netherlands and who conducted one of the controversial genetic engineering studies. Fouchier gets some money from the U. S. federal government but says he can re-start research using funds from the European Union and elsewhere.

H5N1 is still evolving, said Fouchier, and it’s important to understand how and when it might change. They say they can use their findings not only to keep an eye out for when the virus is beginning to get dangerous, but also to help design good vaccines and better drugs to treat flu.

“It is our opinion that in those countries where the research can be done safely, the research should start,” Fouchier said. “We simply need to re-start our research.”

“We want the world to be better prepared than we currently are when the  H5N1 virus causes a pandemic,” Kawaoka agreed. “We believe the benefits of H5N1 research outweigh the risks and that is why we need to resume.”

Arthur Caplan, the head of the Division of Medical Ethics at NYT Langone Medical Center and an NBC News contributor, said it's important for researchers to learn what can make H5N1 more virulent or contagious to be better prepared in the case of a pandemic but "the real issue is where they are publishing it and who gets to see it. I have no issue with restarting the research but some issue with where they are going to publish it and where they present it because bad guys can use it too."

One thing the controversial studies found was that it only takes nine genetic mutations for H5N1 to turn from a virus that mostly infects birds into one that can easily infect mammals – including, almost certainly, humans. “Nine mutations for influenza viruses is almost none,” Kawaoka said.

While H5N1 rarely infects people, it causes regular outbreaks among chicken flocks in Asia and the Middle East, and it infects many ducks without causing any symptoms at all. As long as an influenza virus exists in an animal, it will be steadily mutating and also swapping genes with other viruses.

That’s what happened with H1N1 swine flu, which caused a pandemic in 2009. It was a never-before-seen mixture of human, pig and bird viruses. It wasn’t nearly as deadly as other new flu viruses that cause pandemics, something that could lead people to believe that flu pandemics aren’t that big a deal. But H5N1 is a completely new virus to the human body – one reason it kills such a high percentage of its human victims.

Related stories:

Bird flu more common and less deadly than believed

Bird flu mutations make it more contagious

Bird flu experiments should go on, bioethicist says

Don't miss the latest health news at NBC News.com

Mario Tama/Getty Images

Phamacist Prakash Deshpande injects Judith Echevarria with influenza vaccine at a Manhattan pharmacy. Americans are clamoring for influenza vaccine thanks an an unusually early flu season this year.

Drugs stores running out of vaccine. One company’s supply nearly sold out. An unusually early flu season has Americans clamoring for vaccines and all of a sudden they are scarce.

Yet back in September, public health officials were begging people to get vaccinated. Why the disconnect?

There are four main reasons:

• Flu vaccine is hard to make and it takes months
• Americans are ambivalent about vaccines in general and only want flu vaccines when they are scared (like now)
• Doctors are not paid to encourage and remind patients to get a flu shot, and they are afraid to order too much in case they’re stuck with the extra
• Vaccine makers only want to make as much as they can sell and last year the U.S. threw away 30 million doses

It may be 2013, but the United States still uses technology developed in the 1940s to make flu vaccines. In fact, the process for making next year’s flu vaccine is just starting to gear up right now, even though this year’s flu season is nowhere near to being over.

Experts have to first predict which strains of flu virus will be circulating next year. Influenza mutates all the time and there are different strains, so this is tricky. It’s also the reason people have to get a new flu vaccine every year.

The virus must be isolated from patients’ blood, purified, and injected into chicken eggs to grow. These aren’t just any chicken eggs, either – they have to be fertilized, have a chicken embryo inside and they need to be a certain size. The process is fraught with danger and often breaks down if eggs don’t develop right or if there’s contamination.

Then the virus is purified and made into vaccine. New technology is in the works and Novartis now makes flu vaccine at a factory in Holly Springs, North Carolina, using dog cells instead of eggs—a process that’s slightly faster, easier to control and that can be scaled up more quickly.

The hope is for a universal flu vaccine – one that would work against all strains of flu and protect people for years at a time, but progress is slow.

“A vaccine that would provide protection against all of the known strains of influenza has been a goal since flu vaccine was discovered,” says Dr. John Treanor, a vaccine researcher at the University of Rochester in New York. “It’s not going to be a straightforward, easy shot.”

In the meantime, companies predict how much demand there will be months before flu season even starts, and there’s no way to ramp up production when a season like this one hits and there’s suddenly a surge in demand.

This leads to the next problem: Americans don’t like getting flu shots. It’s the main reason demand is hard to predict. About 128 million people, or about 42 percent of the U.S. population, got immunized against influenza last year. That’s even though the Centers for Disease Control and Prevention says everyone over the age of six months should get a vaccine – every year. More than 30 million doses of flu vaccine never got used and were almost certainly thrown away, according to CDC.

“If people followed the recommendations every year, there would be no shortages,” says Dr. Walter Orenstein of Emory University’s Emory Vaccine Center and a former head of the CDC’s immunization program.

“The first issue is that Americans are pretty deeply divided on whether they think flu vaccination is a good idea,” says Katherine Harris, a RAND Corporation economist who studies flu vaccine issues.

“There are the people that get it and the people that don’t, and the people that don’t get it have pretty bad attitudes about it.”

And people aren’t afraid of the flu, even though it kills as many as 36,000 people in a bad year, including 100 children every year. Flu puts as many as 200,000 people into the hospital every year. But in some years it may be a mild season and kill 4,000 people. This variation lulls people into thinking flu isn’t a problem. “Many people who don’t get flu vaccine don’t get it because they don’t feel they, personally, are at risk,” Treanor says.

The flu vaccine isn’t perfect, either, leading many to think it’s a waste of time to get one. This year’s is only 62 percent effective. On top of that. lots and lots of viruses act like flu – causing coughing, headache, muscle aches and so on – so  many people believe they have flu even if they don’t. But Orenstein says if 80 percent of Americans got vaccinated with this vaccine, it would provide “herd immunity” against flu.

“I have had in the last three weeks two respiratory illnesses,” Orenstein says. “And I was vaccinated. But even if one was the flu, the other one was not. Maybe neither of them was flu.” But such uncertainty can make people doubtful about the value of vaccination.

The belief that flu vaccine causes flu is still rampant, although doctors all agree it’s not true. Many people also fear side-effects from the vaccine. Vaccine regulators and public health experts still remember the 1976 swine flu debacle, when the U.S. government rushed out a mass immunization against a swine flu virus that never spread off one military base.

Several hundred cases of a rare neurological disease called Guillain-Barre syndrome were reported afterward and the incident made many people mistrustful of immunizations.  More recent fears center on a mercury-based preservative called thimerosal, which was taken out of most vaccines after activists claimed it could cause autism. The link is discredited by many scientific studies but suspicion persists among some parents and activists.

Harris says people do trust their personal physicians, but doctors are not usually paid by health insurance companies to talk people into getting flu vaccines, and they aren’t paid much to administer them. Doctors have to compete with pharmacies, big companies that buy up vaccine to give to their employees, and large stores like Wal-Mart and Target to even get vaccine to stock, and they have to eat the cost if they don’t sell all the vaccines they buy to patients.

“It is a cost that comes right off their books,” Harris says. So many don’t even bother.

“We don’t really have a way for compensating health care providers for encouraging us to take preventive steps,” she said. The 2010 Affordable Care Act does have provisions for rewarding preventive medicine, however, which take effect in 2014.

Harris believes that if doctors’ offices worked harder to remind people to get a flu shot, more people would get it, vaccine makers would provide more supply, and flu shot shortages would ease up.

The Trust for America's Health agrees. It recommends that insurers be required to cover flu vaccines under public and private insurance without cost-sharing.  "For instance, currently, 12 states and Washington, D.C. do not require Medicaid to cover flu shots with no co-payment requirements for beneficiaries under the age of 65," the group said in a statement released Tuesday.

The federal government is trying to help in other ways, too. Ten years ago, just four companies made flu vaccines. This year, the U.S. government has licensed vaccines made by seven manufacturers. They include a nasal spray that’s been shown to work especially well in children and a special formulation for older people, whose immune sytems don’t respond as well to vaccines.

The idea is to spread the risk as well as to increase availability. Sanofi Pasteur, which provides about half of the flu vaccine in the U.S., says it has sold out of four of its six formulations of its Fluzone seasonal flu vaccine because of late-season demand.

Companies are wary of making too much vaccine, however, because they can’t re-sell it next year. The flu strains will likely have changed enough to make this year’s vaccine out of date for next year. “It’s not like you can carry it over if you don’t use it,” says Orenstein.

In 2008-2009 the U.S. government shipped 162 million doses of vaccine, but only 90 million were used. And last year 30 million doses or more went unused – most at a loss to the drug makers.

As a result, this year the seven companies made 135 million doses of flu vaccine. So far 128 million have been distributed to pharmacies, doctors’ offices and other providers.

“We have received reports that some consumers have found spot shortages of the vaccine,” Food and Drug Administration commissioner Dr. Margaret Hamburg says in her blog. “We are monitoring this situation and will update you at our Website and at www.flu.gov.” There’s a flu vaccine finder on those websites.

“The flu season usually peaks in January or February, but can extend as late as May,” Hamburg adds – meaning it’s not too late to get a vaccine if you can find one.

“All of us should be encouraging our friends, our neighbors – everyone – to get vaccinated,” Orenstein said. 

• Related links:
• Nasty flu season sparks shortages
• Flu shot isn't perfect
• Flu shot still a hard sell
• Teen death shows flu can kill

MIXA via Getty Images stock

You may think your cough ought to last no more than a week, but the actual duration of a typical cough is nearly 18 days, and could be more than three weeks, a study finds.

If you’re a victim of this year’s terrible flu, or any of the other nasty bugs causing general respiratory distress, Dr. Mark Ebell sends his sympathies.

But if you’re tempted to head to the doctor to demand drugs for the hacking cough that came with your illness, he’s got another message: Wait a little longer.

A new study shows that although most people think a cough ought to last no more than a week or so, the duration of the most annoying symptom of winter illness is about 18 days -- and could be more than three weeks.

Taking antibiotics in the interim is not only ineffective, it could also prompt dangerous side effects -- and contribute to the country’s growing problem with bugs becoming resistant to the drugs used to treat them.

That’s according to a new study by Ebell, an associate professor at the University of Georgia College of Public Health, which sought to define the gulf between public perception and reality when it comes to coughing.

“A lot of times patients will come to me and they’ve been coughing for four or five days and they’re not getting any better, so they ask for an antibiotic,” he said. “After eight or nine days, they’re still not feeling better, so they ask for an even stronger antibiotic. Then they’ll say, ‘The only thing that really works for me is this really strong antibiotic.’”

The trouble is, antibiotics aren’t actually the solution for most of the 3 million outpatient cases in the U.S. each year in which cough is the chief complaint, or for the more than 4.5 million outpatient cases diagnosed as acute bronchitis or bronchiolitis. More than 90 percent of such cases are viral, not bacterial, which means they won’t respond to the drugs most folks request, according to the Centers for Disease Control and Prevention.

Ebell decided to pursue the study, published Monday in the journal Annals of Family Medicine, after noticing the disconnect between how long people thought coughs should last and how long they actually lingered.

When he surveyed nearly 500 Georgia residents by phone, he found that they predicted that a cough would last between five days and nine days, but generally about a week, depending on the scenario.

A review of 19 published medical studies, however, revealed that the mean duration of any cough was 17.8 days, with a range of 15.3 to 28.6 days.

If a person demanded -- and received -- an antibiotic after he or she had been sick for a week,  the condition might improve several days later -- but not because of the drug, Ebell said.

“Although this outcome may reinforce the mistaken idea that the antibiotic worked, it is merely a reflection of the natural history of acute cough,” he said.

Convincing people of that fact is tough. In Ebell’s study, a quarter of participants thought that antibiotics were "always helpful" and about 44 percent said they were "always or usually" helpful. 

That ignores the reality that antibiotics won't affect viral infections, and also that they can cause harmful side effects, including allergic reactions and the life-threatening gut condition called C. difficile, Ebell said. Plus, overuse of antibiotics is contributing to conditions such as drug-resistant pneumonia and other infections.

Crystal Thompson, a 34-year-old kindergarten teacher in Fort Worth, Texas, says that she’d start to become concerned if a cough lasted more than a few days.

“I would think no longer than a week,” said Thompson, whose family is just now getting over this year’s severe flu. “If it lasted longer than a week, I’d be in to the doctor.”

But Thompson said she also understands the difference between a viral infection and a bacterial one and that she’d follow her doctor’s advice about antibiotics.

In general, Ebell said he tells patients that they likely don’t need an antibiotic unless symptoms turn serious, with shortness of breath, high fever or bloody or rusty phlegm.

It’s important to get the message out about the actual duration of a normal cough, said Dr. Gustavo Ferrer, director of the new cough clinic at the Cleveland Clinic’s Weston, Fla., site. Ferrer, who was not involved with Ebell’s study, praised it as “beautiful” way to remind the public that there’s not a drug solution for every symptom.

“We have come to the conclusion as a population that we don’t want to be sick for one hour,” he said. "In reality, people want those symptoms to go away right away."

Still, cough docs know that patients come for some relief. Ferrer said that antihistamines such as Benadryl can help dry up airways, reduce coughing and help people sleep. Cough drops – especially those with honey and herbs – can help during the day, he added.

Ebell said he and other docs have come up with a range of ways to discourage demand for antibiotics. They’ll call the infection a “chest cold” instead of acute bronchitis. They’ll agree to write an antibiotic prescription -- but then tell patients to wait.

“If you feel that you’re really not going to get them out of the office without a prescription, give them one and say ‘Don’t fill it for a few days,’” he said. “About half never fill it at all.”

Related stories: 

• 5 things do to (and 5 not to do) when you have the flu
• Flu spreads to 47 states, but may be waning
• Flu jab isn't perfect by a long shot, health officials admit

The nation’s nasty flu season has created a sudden surge in demand for vaccine, leaving some sites across the country short on the shots that can prevent illness -- or make it a little less miserable.

There’s still enough vaccine to go around, but people may have to make a few calls to get it, said Tom Skinner, a spokesman for the Centers for Disease Control and Prevention.

“We understand there are some spot shortages here and there,” Skinner said. “People have taken note that we’re experiencing a moderate to severe season.”

That message was echoed by Walgreens, one of the nation’s largest drugstore suppliers of flu vaccine.

“Due to increased demand for flu shots in recent weeks, select locations may currently be experiencing shortages in supply of flu vaccine,” said Robert Elfinger, a company spokesman.

Walgreens is working on ensuring a steady supply and plans to be able to continue offering flu shots through the season.

Sanofi Pasteur, which provides about half of  the flu vaccine in the U.S., told NBC News on Thursday that it had sold out of four of its six formulations of its Fluzone seasonal flu vaccine because of late-season demand for vaccines. The company still has other vaccines available for adults and children, officials said.

On Twitter, some flu-wary patrons have been posting their frustrations:

“Heard the flu shot is spreading like never before, had to call 5 places to find the flu shot in stock. I am vaccinated,” one shot-seeker wrote.

As of Jan. 4, more than 128 million doses of flu vaccine had been distributed across the country, according to latest CDC figures. That’s out of 135 million produced for this season.

There’s no word yet on how many people actually have been vaccinated; by the end of November, about 112 million people in the U.S. had received shots, but that number likely has risen sharply.

That’s because this year’s flu season started early and includes a virus that causes unusually severe illness. Flu has now spread to more than 80 percent of the country, the CDC said.

Related: Are you worried about missing work if you or your kids get the flu?

The agency will issue new figures on Friday, but latest reports indicated that more than 2,200 people had been hospitalized since October and 18 children had died.

This year’s flu vaccine is a good match for the circulating viruses, CDC has said. It covers two strains of influenza A and one strain of influenza B. However, a second B strain is not covered and may be accounting for 8 percent to 10 percent of illnesses, infectious disease experts said.

One good way to find flu vaccine nearby is through the HealthMap Vaccine Finder. The site includes some 40,000 locations across the U.S. Users can plug in their addresses or ZIP codes and find which sites are offering vaccine.

There’s still time to get the vaccine, which can prevent illness – or at least shorten its duration and severity. It takes two weeks for immunity to build up after the shot, so health officials are encouraging people to take action now.

There’s really no shortage of the shots, just some local disruptions in supply, said Erin Fox, manager of the Drug Information Service at the University of Utah, which tracks drug shortages.

“Tons of flu vaccine still available!” Fox says.

Reuters contributed to this report. 

Related stories: 

• Bad flu season worsens as Boston declares emergency
• Early flu season accelerates; no peak yet
• How to protect yourself from the flu? Wash your hands