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Researchers explore future of influenza vaccines
Nabel GJ. Nat Med. 2010;16:1389-1391.
Treanor JJ. Vaccine. 2010;28:8268-8274.
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Making a universal influenza vaccine that confers decades-long protection from any influenza virus strain is feasible, but licensing it may require innovation on several fronts, including finding new ways to evaluate the efficacy of vaccine candidates in clinical trials, researchers for the National Institute of Allergy and Infectious Diseases said.
Currently licensed influenza vaccines elicit antibodies directed at the influenza surface protein hemagglutinin, but its composition changes from year to year, forcing continued changes to influenza vaccines, Anthony S. Fauci, MD, NIAID director, and Gary J. Nabel, MD, PhD, director of the NIAID Vaccine Research Center, wrote in a Nature Medicine commentary.
A universal influenza vaccine would have to elicit a type of immune response that rarely occurs naturally, Fauci and Nabel wrote.
A detailed understanding of virus structure may make such a vaccine possible. For example, scientists have identified a region of hemagglutinin’s stem that is shared among diverse strains, and a research group at NIAID’s Vaccine Research Center recently created influenza vaccines that elicit antibodies aimed at this shared region, rather than at hemagglutinin. Animals that received the experimental vaccines were protected from a diverse array of influenza strains, Fauci and Nabel wrote.
Fauci and Nabel also sorted the 16 known influenza virus subtypes into three tiers based on their likelihood of causing widespread disease in humans, and they said vaccine development may be prioritized to produce first-generation universal influenza vaccine candidates that protect against multiple virus strains within the highest priority group.
In another article, published in Vaccine, researchers from the University of Rochester reported on an innovation in influenza vaccination development; specifically, an experimental vaccine grown entirely in bacteria. Researchers from the University of Rochester Medical Center said the process used to develop the vaccine bypasses the egg completely, which is an important step to mass-producing vaccines in a more cost-effective fashion.
John Treanor, MD, and colleagues said the vaccine, which was tested in 128 healthy adults, works well in people, triggering an immune response that would protect them against influenza. The vaccine, which is free of bacteria itself, is manufactured by VaxInnate Inc., which funded the study.
“There are a number of problems with using eggs to produce flu vaccine,” Treanor said in a press release. “It’s a very specialized product. It’s hard to make more eggs in a hurry — you only get them as fast as hens lay them. They’re not easy to manipulate, and it can be challenging to get the flu virus to grow within an egg. The flu vaccine system would be more flexible and reliable if we didn’t have to rely on them.”
In this vaccine, the researchers focused on one small key protein of hemagglutinin that can be correctly refolded after synthesis in bacteria, Treanor said. The small protein is enough to spur the immune system because it was attached to an adjuvant. Currently, adjuvants are not part of US influenza vaccines, although they are used in other countries and as parts of other vaccines.
For someone who has been advocating for influenza vaccination of children for over 30 years, I can honestly say that some very exciting new prospects for influenza vaccines are on the horizon. First, as outlined in this article, alternative approaches to growing influenza vaccines in eggs are being hotly pursued. The threat of avian influenza wiping out flocks of chickens and making vaccine production impossible has stimulated a number of new and innovative approaches to vaccine production. Classical cell cultures systems are being used to grow vaccine strains as well as recombinant vaccine antigens are being produced in plant, insect and bacterial cells. These vaccines will need to produce products that have the correct conformational structures so they mimic natural influenza strains to be optimally protective. Such products are under study.
As also outlined in this article, the need to immunize each year with a combination of influenza strains predicted to circulate that year, also poses formidable challenges. Projections by even the most sage advisors to the WHO and FDA may not predict the correct strains that will circulate. In addition, no other vaccine must be administered each year to all the population. This poses additional obstacles. Even more problematic in young children who have not been previously primed with influenza vaccine, these children need two doses within the short time before influenza circulates. Thus, the potential for a vaccine that is more “universal” that can protect against a broader array of antigens and not need to be administered each year is very attractive. The NIH group and several other research groups throughout the world are pursuing this approach.
Finally, the addition of new oil-in-water adjuvants added to influenza vaccines have been evaluated in children in Europe and Canada and they have found to be very immunogenic and highly protective for the prevention of both pandemic H1N1 and seasonal influenza strains. This approach will need to be more extensively evaluated for efficacy and safety, but may be the needed boost that influenza vaccines need to increase their efficacy substantially. So in summary, there are many new exciting approaches for the prevention of influenza infections and each of them should be vigorously investigated.
—Kathryn M. Edwards, MD
Infectious
Diseases in Children Editorial Board member
Dr. Edwards has no relevant disclosures to report.
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