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Vaccine Shown Effective Against Range of Flu Viruses

H1N1 virus

Electron-microscope image of the 2009 H1N1 influenza virus (CDC.gov)

25 January 2018. An experimental vaccine made with protein-infused nanoscale particles was shown to provide long-lasting protection in lab mice against a broad range of common influenza viruses. Researchers from Georgia State University in Atlanta describe their vaccine in yesterday’s issue of the journal Nature Communications.

The Georgia State team, led by molecular biology and biochemistry professor Bao-Zhong Wang, is seeking better tools to contain and prevent the contagious viral disease influenza or flu. The virus causing flu outbreaks has two main types known as influenza A and B. Influenza A viruses emerge as different strains from the composition of proteins on their surface, called hemagglutinin and neuraminidase, abbreviated to H and N. The various influenza A strains are made up of combinations of 18 H and 11 N proteins, with H1N1 and H3N2 among the most common flu viruses this year. Influenza B has just two main sub-types.

The continuous mutation of flu viruses, particularly influenza A, make the disease difficult to contain from year to year. Different flu strains emerge each annual flu season, and public health authorities need to prepare well in advance to anticipate the strains likely to arrive, then develop, produce, and distribute seasonal vaccines to protect against those strains. If the annual predictions miss the correct mix of influenza strains, the seasonal flu vaccines are less effective. That situation appears to be occurring in the current (2017-2018) flu season in the U.S., with 49 of 50 states reporting cases of flu and 32 states, plus New York City and Puerto Rico, noting high flu activity rates, as of 13 January 2018.

To help solve this problem, Wang and colleagues, including associates from Emory University and Georgia Tech, are developing a vaccine that can apply to a wide variety of flu viruses, and provide immunity for extended periods. The researchers are focusing on the hemagglutinin proteins that vary considerably in the influenza A virus. While current vaccines aim at the variable parts of the protein’s head region to prevent infections, the researchers instead target the less variable stalk of the protein’s chemistry.

While the stalk portion of the H protein may be less variable, it is also not stable and easily degraded. Thus, to create a vaccine that would induce continuous immunity triggered by the protein’s stalk region, the team turned to nanoscale particles for delivering an antigen to induce a response from the stalk protein’s chemistry. Wang identified this antigen known as matrix protein 2 ectodomain, or M2e, in an earlier study. The nanoparticles are double-layered with M2e proteins to extend their activity time in the body.

“We assembled this stalk domain into a protein nanoparticle as a vaccine,” says Wang in a university statement. “Once inside, the nanoparticle can protect this antigenic protein so it won’t be degraded. Our immune cells have a good ability to take in this nanoparticle, so this nanoparticle is much, much better than a soluble protein to induce immune responses.”

The researchers tested the nanoparticle vaccine with 2 injections in lab mice, and exposed the mice to lethal doses of four influenza A viruses: H1N1, H3N2, H5N1, and H7N9. After 4 weeks following the second injection, mice receiving the vaccine survived without respiratory effects, while comparable mice receiving a placebo suffered lung infections, severe weight loss, and death.

The team believes its study shows the technology can provide the basis for a universal flu vaccine, subject to further preclinical testing and human clinical trials. The authors also note that its formulation with nanoscale particles would not likely require refrigeration, making it easier to store and ship in many regions.

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