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2010 NIAID Year in Review

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Promising Strategies to Combat Diverse Flu Strains

New Strategy Advances Progress Toward a Universal Flu Vaccine

The emergence and rapid spread of the H1N1 influenza virus in 2009 made clear the need for a “universal” flu vaccine—one that could protect for decades against multiple, if not all, flu strains. In 2010, scientists with the NIAID Vaccine Research Center brought this concept closer to reality with a two-step immunization approach that elicited infection-fighting antibodies against a range of flu virus strains when tested in mice, ferrets, and monkeys. The researchers first primed, or activated, the animal’s immune systems with a vaccine made from DNA encoding the flu virus's hemagglutinin (HA) surface protein. The animals then received a booster dose of the 2006–2007 seasonal influenza vaccine.

The researchers found that although the DNA in the priming vaccine was derived from a 1999 flu virus, the animals produced antibodies capable of neutralizing a wide range of flu virus strains, including those from 1934, 2006, and 2007. Although the prime-boost vaccines were made from H1 subtypes of influenza A, they also neutralized other types of flu, including H5N1 avian influenza, suggesting that a prime-boost strategy could protect against many or all subtypes of influenza A. Further analysis of the neutralizing antibodies revealed that they targeted a portion of the HA protein that varies little from strain to strain, giving hope that this prime-boost vaccine strategy could confer immunity against multiple flu strains.

Clinical trials are currently under way in humans to test the safety and efficacy of prime-boost influenza vaccines.

Reference: Wei CJ, Boyington JC, McTamney PM, Kong WP, Pearce MB, Xu L, Andersen H, Rao S, Tumpey TM, Yang ZY, Nabel GJ. Induction of broadly neutralizing H1N1 influenza antibodies by vaccination. Science. 2010 Aug 27;329(5995):1060-4.

Drug Shows Promise Against Pandemic Flu Strains

Camp Funston
Photograph of an emergency hospital at Camp Funston, Kansas, that cared for large numbers of soldiers sickened by the 1918 flu. Credit: National Museum of Health and Medicine, Armed Forces Institute of Pathology, Washington, D.C. Image number NCP 1603

To combat new and resistant influenza strains, additional antiviral approaches are needed. The drug Fludase (DAS181), a synthetic protein developed to prevent entry of flu viruses into respiratory cells, has shown activity against various human seasonal flu viruses as well as potentially lethal avian flu strains. Investigators recently studied the effectiveness of Fludase against several pandemic H1N1 influenza viruses, including the 1918 pandemic strain. They found that the drug stopped replication of the pandemic flu strains in cell culture models, and it protected mice from pandemic flu disease. Its antiviral activity against pandemic influenza strains was about the same as against seasonal flu virus, including seasonal flu strains that are resistant to oseltamivir (Tamiflu). These results suggest that Fludase may provide protection should pandemic viruses, such as H1N1, develop resistance to Tamiflu. NIAID is currently supporting clinical trials to study the effectiveness of Fludase in treating non-complicated influenza infection.

References

Triana-Baltzer GB, Gubareva LV, Klimov AI, Wurtman DF, Moss RB, Hedlund M, Larson JL, Belshe RB, Fang F. Inhibition of neuraminidase inhibitor-resistant influenza virus by DAS181, a novel sialidase fusion protein. PLoS One. 2009 Nov 6;4(11):e7838.

Triana-Baltzer GB, Gubareva LV, Nicholls JM, Pearce MB, Mishin VP, Belser JA, Chen LM, Chan RW, Chan MC, Hedlund M, Larson JL, Moss RB, Katz JM, Tumpey TM, Fang F. Novel pandemic influenza A (H1N1) viruses are potently inhibited by DAS181, a sialidase fusion protein. PLoS One. 2009 Nov 6;4(11):e7788.

Last Updated November 10, 2011

Last Reviewed June 03, 2011