Potential universal flu vaccine identified

By John Murphy, MDLinx
Published December 8, 2015

Key Takeaways

Rather than trying to predict which influenza virus strains are likely to cause human disease and then make a vaccine to match those specific strains, investigators at the National Institute of Allergy and Infectious Diseases (NIAID) in Bethesda, MD, have created a vaccine cocktail that provides broad protection against a wide variety of lethal influenza A virus infections in mice.

This promising discovery could eventually lead to a universal flu vaccine in humans, the investigators said.

In this study, the NIAID researchers used a non-infectious virus-like particle (VLP) vaccine cocktail that incorporated 4 different subtypes (H1, H3, H5, and H7) of hemagglutinin, a key surface protein of the influenza virus.

“There are 16 different hemagglutinin subtypes that circulate in birds and are thought to be the basis for current and future influenza pandemics," said principal investigator of the study Jeffery Taubenberger, MD, PhD, Chief of Viral Pathogenesis and Evolution Section, Laboratory of Infectious Diseases at NIAID. "The hypothesis was that the presentation of these different viral proteins would stimulate the development of cross-protective immunity that would provide broader protection against multiple subtypes."

The researchers picked the H1 and H3 subtypes because they have been the major cause of human seasonal flu outbreaks since 1918. They chose the H5 and H7 subtypes because they have been the cause of recent bird flu outbreaks and have pandemic potential. This selection also provided a broad representation of hemagglutinins across the phylogenetic tree, the researchers noted.

In a series of experiments, they found that 95% of mice vaccinated with the investigational cocktail were protected against a lethal challenge of 8 different influenza strains expressing 7 different influenza A subtypes, compared with only 5% of mice who received mock vaccinations.

"Almost all of the animals that were vaccinated survived, including mice that were challenged with viruses that expressed hemagglutinin subtypes that were not in the vaccine at all—viruses that expressed H2, H6, H10, and H11," Dr. Taubenberger said. "What that suggests is that this approach really gives us broad spectrum protection, and could serve as a basis for an effective pre-pandemic vaccine."

Additional experiments showed that the vaccine was durable, effective for at least 6 months, and that it worked well in older mice. This is important given that elderly people are particularly susceptible to severe disease following influenza infection, and current vaccines are less efficacious in the elderly than in younger people.

The investigators are now testing the VLP cocktail in ferrets. If the results are similar to those seen in mice, they will advance the vaccine into early-stage human clinical trials.

For more information visit the MDLinx Influenza Resource Center.

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