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NIAID Researchers Advance Development of Universal Flu Vaccine

Colorized transmission electron micrograph showing  H1N1 virus particles. Surface proteins on the virus particles are shown in  black.
Colorized transmission electron micrograph showing H1N1 virus particles. Surface proteins on the virus particles are shown in black.
Credit: NIAID

Background

Seasonal flu vaccines work by generating antibodies that target the head region of hemagglutinin (HA), a glycoprotein found on the surface of the influenza virus. The head region is subject to mutations, leading to a constant variation in viruses. As a result, vaccines are updated annually to best target the viruses most likely to spread and cause illness in a given flu season.

Scientists have been working for years on a universal flu vaccine, or a vaccine that confers protection against all influenza viruses, including unrelated subtypes that infect animals and can be transmitted to humans. One possible approach is to create a vaccine that would elicit antibodies targeting a different part of the HA glycoprotein: the stem. Unlike the head, the HA stem is less likely to mutate and remains consistent across strains of flu within a particular hemagglutinin group. If this type of immunity can be elicited, then in theory, a vaccinated person could be protected against future seasonal strains of influenza virus and have at least partial protection against future pandemic strains.

Scientists from the Vaccine Research Center (VRC) and the Laboratory of Infectious Diseases at NIAID, part of the National Institutes of Health, developed a nanoparticle vaccine with a stabilized HA stem from an H1N1 influenza virus. The vaccine lacks the HA head region to more effectively stimulate antibodies that hitch themselves to the stem.

Results

Investigators immunized mice and ferrets with the experimental vaccine based on sequences from H1 and subsequently challenged the animals with a lethal dose of H5N1 influenza. The vaccine elicited cross-reactive antibodies that completely protected mice and partially protected ferrets against significant disease. It is important to note that the vaccine was created from an H1 HA stem but elicited protection against a different HA subtype (H5) (heterosubtypic protection). While the vaccine did not elicit broadly neutralizing antibodies, protection was shown to be antibody-mediated. Investigators injected antibodies from the immunized mice into non-immunized mice, and protected mice against a lethal challenge with H5N1 influenza. This confirms that the antibodies served to protect the mice. Together, the results provide proof-of-concept that a vaccine that elicits antibodies that target the HA stem can offer broad protection against diverse influenza strains.

Next Steps

Moving forward, investigators may make additional refinements to the vaccine to improve its ability to elicit cross-reactive neutralizing antibodies and binding antibodies. In addition, they will work on a similar approach to protect against viruses with group 2 hemagglutinins. Investigators will also work toward a Phase 1 clinical trial to test the vaccine for safety and immunogenicity in humans. If both are demonstrated, this vaccine concept could move into larger-scale efficacy studies.

Reference

Yassine H et al. Hemagglutinin-stem nanoparticles generate heterosubtypic influenza protection. Nature Medicine. DOI:10.1038/nm.3927 (2015).​

Last Updated August 28, 2015