Proposal for prepandemic vaccination sparks discussion

May 13, 2010 (CIDRAP News) – An influenza expert who formerly headed the World Health Organization's (WHO's) flu program and now works for Novartis has suggested developing a prepandemic vaccine to get the jump on the next flu pandemic—an idea that other experts are greeting with caution or skepticism.

Dr. Klaus Stohr, former director of the WHO's Global Influenza Programme, proposes developing a vaccine containing a "cocktail" of flu strains deemed likely to cause the next pandemic, along with an adjuvant (immune-system stimulant). He presents the idea in an opinion article released online yesterday by Nature.

The idea of prepandemic vaccination has been around for years, fueled by some studies suggesting that adjuvants can make flu vaccines protective against more than just the specific viral strain they are based on. But because of the many uncertainties facing such an approach—including safety questions and the unpredictable timing of pandemics—it has never gained much traction.

Stohr says prepandemic vaccination would help address the problem that when a pandemic virus emerges, it takes about 6 months to develop and produce a well-matched vaccine for it—as was demonstrated last year with the pandemic H1N1 virus. He says this approach could also help mitigate the huge shortage of production capacity to meet global needs.

Stohr is vice president of influenza strategy at Novartis Vaccines and Diagnostics in Cambridge, Mass. The company makes flu vaccines and the adjuvant MF59, which is used in the Focetria vaccine for pandemic H1N1, licensed in Europe.

"An increasingly discussed method is to immunize people against pandemic-type viruses before a pandemic strikes," Stohr writes. "This could limit the spread of the virus in the early stages of a pandemic and significantly reduce the peak demand for vaccine. It would thus free up supply for countries where vaccination is patchy, or that do not have the infrastructure or budget to purchase any vaccine."

He suggests a prepandemic vaccine could contain H2, H5, H7, and H9 flu subtypes, plus adjuvants "designed to provoke a long-term immune response to a range of virus subtypes, even viruses different from the original strain."

Stohr says prepandemic vaccine could be added to or given along with seasonal flu vaccines in countries where seasonal vaccination is recommended for nearly everyone. Another option, particularly for developing countries, would be to include the prepandemic vaccine in routine childhood immunizations, he writes.

He acknowledges that few public health leaders take the idea of prepandemic vaccination seriously but says it deserves careful study. "I invite those who find it unsurprising that an employee of a leading vaccine producer holds this view to come up with alternative solutions to the sobering reality of 'too-little-too-late' supply" in the event of a pandemic, he states.

Views of other experts
Other experts who spoke with CIDRAP News about Stohr's article agreed that new approaches are needed to solve the problem of providing pandemic flu vaccines, but they said the strategy would face serious obstacles, including possible public rejection of an adjuvanted vaccine against an uncertain future threat.

Dr. Gregory A. Poland, director of the Mayo Clinic's Vaccine Research Group in Rochester, Minn., said, "I think he's right in raising an important issue, and it's worth study and consideration, recognizing that it would raise a host of scientific questions that would have to be answered before we embark on it. . . . The thinking is right in that we need to do something innovative, because what we know to do is insufficient."

He said one form of prepandemic vaccination that might be considered would be to include a vaccine against one potential pandemic subtype in the seasonal flu vaccine each year, along with an adjuvant.

Including an adjuvant in the vaccine would be necessary because otherwise it would not generate sufficient long-term immune memory, Poland said. But using an adjuvant would raise safety questions, since adjuvanted flu vaccines have not been used widely, and not at all in the United States.

He said the public is likely to be skeptical about the need for and safety of a prepandemic vaccine. The pandemic H1N1 vaccine "was basically identical in safety to standard seasonal vaccine, and yet all sorts of safety misconceptions and fears were widely promoted, with no evidence," he commented.

Michael T. Osterholm, PhD, MPH, public health expert and director of the University of Minnesota Center for Infectious Disease Research and Policy, which publishes CIDRAP News, called Stohr's suggestion "not really practical."

One problem is that a vaccine against a given flu subtype does not guarantee protection against another strain of the same subtype, as was demonstrated in the H1N1 pandemic, he said. Vaccination against the seasonal H1N1 virus was not found to confer significant protection against the pandemic virus.

As to the assertion that adjuvants may provide some protection against flu strains other than what's in the vaccine, Osterholm said, "But the problem is that even if this is scientifically true, we learned [in the H1N1 pandemic] that the use of adjuvants might be a major deterrent to a large segment of the population even taking the vaccine, because of safety concerns." (In Europe, public reluctance to take the H1N1 vaccines was attributed in part to the use of adjuvants, which were seen as a new technology.)

Further, the production capacity to make a prepandemic vaccine is lacking, and it's not clear that money would be available. "I'm not convinced at this point that if you launched such a program the funding would be there," he said.

"I think the bottom line is we need new influenza vaccines that have heterotypic [broader] subtype protection, but I'm not convinced that they're going to be the same old vaccines," Osterholm said. He said that goal may require a vaccine that targets a viral comoponent other than the traditional antigen, hemagglutinin, and that induces both humoral and cellular immunity.

John Treanor, MD, a vaccine researcher at the University of Rochester in New York, noted that the idea of "priming" the population with a prepandemic vaccine has been under discussion for a while. He is a professor of medicine and of microbiology and immunology.

"There's some data that one thing that could work would be to prime people with a single vaccine now and then boost them with the pandemic strain that could emerge in the future," he said, adding that the priming vaccine could be part of routine immunizations.

Concerning whether adjuvants would make a vaccine sufficiently broadly protective to justify prepandemic vaccination, Treanor said, "I think that's a very complicated question; it's hard to say definitively one way or the other. There's a lot of data that say that adjuvants would be useful. Does that mean we should vaccinate the whole world with adjuvanted flu vaccines? I don't know. These are difficult issues."

From a practical point of view, the biggest advantage of adjuvants is that they lower the dose of vaccine needed, stretching the supply, Treanor said. The use of adjuvants and low-dose flu vaccines could be an important strategy for battling flu in developing countries, he observed.

"There's a good argument to say this [prepandemic vaccination] is the way to go, but you have to realize that he [Stohr] represents a company that makes the adjuvanted influenza vaccine that he's saying should be given to the entire world," Treanor commented.

Stohr K. Vaccinate before the next pandemic? (Commentary) Nature 2010 May 13;465(7295):161

See also:

Oct 31, 2007, CIDRAP News story "The pandemic vaccine puzzle, part 5: What role for prepandemic vaccination?"

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