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The US government's tentative plan to develop a stand-alone vaccine for the swine-origin H1N1 influenza virus could strain the nation's vaccine makers to the point of reducing production of seasonal flu vaccine this fall, an official with the National Institutes for Health told Medscape Infectious Diseases.

It's all a matter of striking a balance between the unknown threat of the H1N1 influenza virus and the known threat of the seasonal flu virus, said Gary Nabel, MD, director of the vaccine research center at the National Institute of Allergy and Infectious Diseases.

"There may have to be compromises," said Dr. Nabel. "We'll know more as time goes on."

Balancing the supply of 2 different vaccines is just one challenge facing public health officials as they contemplate vaccinating Americans against a new flu virus that has resulted in 141 confirmed cases and 1 death in the United States, killed possibly 170 people in Mexico, and emerged in at least 9 other nations. Questions remain for public health officials about whether citizens will go to the trouble of getting both seasonal and H1N1 vaccines and how to reduce potential arguments over who in the general public should be the first to receive vaccination with the limited supplies of H1N1 vaccine in the fall.

Yesterday, Richard Besser, MD, acting director of the Centers for Disease Control and Prevention (CDC), said that the CDC is discussing a plan to manufacture a separate H1N1 vaccine — if it's needed — after completing the production of next fall's seasonal flu vaccine, which is now under way. The alternative, considered unrealistic, would be to delay production of the seasonal vaccine so that the H1N1 vaccine could be incorporated into it.

Vaccine makers would create a 2-dose regimen for the H1N1 vaccine — a primer dose at first, followed by second to "seal the deal," said Christine Layton, PhD, MPH, a public health researcher and influenza pandemic expert at RTI International in Research Triangle Park, North Carolina. To immunize roughly 300 million Americans, therefore, the federal government would need 600 million doses. That's 4 times the number of doses of seasonal flu vaccine that vaccine makers were projected to make for the 2008–2009 flu season, according to the CDC. "Production will be a big challenge," said Dr. Layton.

Can the United States successfully conduct a 2-front war on flu viruses? On the bright side, experts say that our vaccine-making capacity is stronger than ever. During the 2004–2005 flu season, a single company, Sanofi Aventis, was putting injectable seasonal flu vaccines into the immunization pipeline. In 2009, 6 companies are licensed to manufacture seasonal flu vaccines in this country (one of them makes a nasal spray), and all of them are working to expand their production capacity, according to the CDC.

There are other positives. Dr. Nabel said the recipe for this fall's seasonal flu vaccine will contain 2 of the 3 influenza virus strains used in the vaccine for the 2008–2009 flu season, making it easier to produce. That good fortune could help vaccine makers maintain adequate supplies of seasonal flu vaccine while pumping out an H1N1 version, he said.

Manufacturers also can stretch their supply of H1N1 vaccine by adding so-called adjuvants, which amplify the immune response. Growing vaccine-bound viruses in cell cultures as opposed to chicken eggs — the traditional and more cumbersome process — also promises to boost production, but not necessarily in 2009, added Dr. Nabel. "I doubt that it could satisfy the demand that is out there."

All in all, said Dr. Nabel, the production equation depends on how severe the H1N1 virus outbreak turns out to be. To create enough H1N1 vaccine, it may be necessary to cut back on seasonal vaccine production, he said. That prospect troubles experts such as Dr. Layton, since seasonal influenza claims the lives of 36,000 people each year. "It's not an inconsequential disease," she said.

However, stinting on the supply of an H1N1 vaccine creates problems, too. As it is, the federal government envisions having 50 to 80 million doses of the H1N1 vaccine this fall, with the rest of the necessary doses becoming available later in the year as manufacturing continues.

"Early on, when the vaccine is in short supply, the biggest challenge will be determining how it will be administered in a way that's epidemiologically appropriate and ethically sound," said Dr. Layton. Faced with limited quantities, she said, the general public may fight over the vaccine just as shoppers sometimes fight over store merchandise on sale. "It's an unfortunate part of human nature," she said.

To be sure, the US Department of Health and Human Services probably will recommend a pecking order for who should receive any H1N1 vaccine, said Dr. Nabel. HHS took that same approach in gearing up for a possible avian flu pandemic 3 years ago, putting the vaccine and antiviral manufacturing workforce at the top of the list, followed by various types of healthcare workers, and then groups of vulnerable patients such as persons older than 65 years with 1 or more influenza high-risk conditions (not including essential hypertension) and pregnant women.

However, such priority recommendations are subject to debate. While healthy persons aged 6 to 64 years are on the bottom of the list for an avian flu vaccine, some have argued that healthy children should be closer to the top during a pandemic, said Dr. Layton. "Elderly persons — particularly those who are ill — often have minimal immune response to vaccines," she said. "Young children, although potentially healthier than sick elderly persons, are more likely to have a robust immune response to immunization and pose a greater risk of spreading infection. [They] often are infectious for greater time periods than adults and come in contact with more people. As such, there are those who assert that young children are a more reasonable group to receive vaccines than frail elderly," she said.

In addition to competing for production resources, separate seasonal and H1N1 vaccines also may confuse patients. "It will be a challenge for public health officials to explain to people what vaccines they're getting, and what they're good for," Dr. Layton added.

The production and administration problems created by separate vaccines for the seasonal and H1N1 influenza will disappear if public health authorities decide to incorporate an H1N1 vaccine into the seasonal vaccine for the fall of 2010. They would have plenty of time to determine whether they should substitute the H1N1 virus for 1 of the 3 viruses used in the seasonal vaccine design, or whether they should make it a fourth component.

Then again, that's assuming the H1N1 virus becomes the major health threat that people fear. As of now, the federal government is on course to produce a H1N1 vaccine, but it could later nix the idea of mass production if the new virus fizzles out. Making the right decision will be tricky, said Gigi Kwik Gronvall, PhD, a senior associate and immunologist by training at the Center for Biosecurity at the University of Pittsburgh Medical Center in Pennsylvania.

"You don't know what the swine flu will do," said Dr. Gronvall. "Biology is always full of surprises. The data changes from day to day, so you need to keep an eye on what's going on and avoid both overreacting and underreacting. And you don't want politics to influence these decisions."

Source : http://www.medscape.com/viewarticle/702229