Scientists have created a vaccine for experimental use that protects animals from both seasonal and pandemic variants of the influenza virus. Clinical trials of the vaccine are now under development. Next-generation vaccinations for the flu have the potential to replace seasonal choices if they are shown to be safe and effective at protecting against the influenza virus.

A study published in the March 24 issue of Nature details how novel influenza vaccines are designed and how they protect mice, ferrets and nonhuman primates. The work was led by researchers at the University of Washington School of Medicine and members of the Vaccine Research Center at the National Institute of Allergy and Infectious Diseases of the National Institutes of Health.

Existing flu vaccines require seasonal use and usually do not protect against multiple circulating strains of influenza. "Most flu vaccines available today are quadrivalent, which means they are made from four different flu strains. Each year, the World Health Organization predicts the four most prevalent influenza strains, but these predictions are more or less inaccurate. That's why we often end up with mismatched flu vaccines that still help, but are only partially effective." said Daniel Ellis, a research scientist in the laboratory of Neil King, an assistant professor of biochemistry at the University of Wisconsin Medical School.

To create an improved version of the influenza vaccine, the team attached hemagglutinin proteins from four different influenza viruses to customized protein nanoparticles. This approach allows unprecedented control of the molecular conformation of the resulting vaccine and produces an improved immune response compared to conventional influenza vaccines. The new nanoparticle vaccine contains the same four hemagglutinin proteins as the commercially available quadrivalent influenza vaccine, eliciting neutralizing antibody responses to vaccine-matched strains equal to or superior to those found in commercial vaccines in mice, ferrets, and non-human primates. Nanovaccines (not commercial vaccines) can also induce protective antibody responses against viruses not contained in the vaccine formulation.

"Our vaccine does respond strongly to strain-matched viruses, and the additional coverage we see against mismatched strains reduces the risk of flu season," Ellis said.

There are currently drugs and vaccines for the influenza virus. These vaccines include attenuated live virus vaccines and inactivated vaccines against influenza A and B viruses in humans. Since the antigenic structure of wild-type viruses is constantly evolving, the corresponding vaccines must update the paralleled virus seeds annually; once the antigenic structure of the seed virus diverges from that of the wild virus, it will no longer be possible for the vaccine to provide protection. Even if the two do match, there will still be the possibility of escape variants being generated. Typically, eggs that have been fertilized are used to produce influenza vaccines. After the WHO announced the recommended influenza strains for the winter season, vaccine manufacturers began production. In addition to eggs, the EU has adopted Optaflu, a flu vaccine made from animal cells that can satisfy the requirements of diverse mass production and avoid the allergens caused by egg-based vaccine production.

In addition to the use of eggs, mammalian cells, cell culture production, and recombinant protein vaccine, the FDA has authorized the clinical evaluation of a plant-based influenza vaccine.


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