Headless HA: Universal Influenza Vaccine?

Nurses COVID

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This commentary is a little technical but I think most can get the concept of how helpful it be would to not to have to make a new flu vax every year, as well as to have it protect us against all of the different influenzas that are out there.

A serious shortcoming of current influenza virus vaccines is the need to reformulate them every year or two as the virus undergoes antigenic drift. Many virologists have been captivated by the idea of a more universal vaccine that would endure longer, perhaps a decade or more. The identification of a conserved domain in the stalk region of the viral HA protein that gives rise to antibodies that block infection by 10 HA subtypes was a step in this direction. The next phase in the development of a new vaccine, the production of an antigen that confers broader protection, has been achieved using an HA molecule lacking the globular head

The vast majority of antibodies that block influenza virus infection are directed against the globular head of the HA, the protein essential for attachment to and entry into cells. Unfortunately, the HA head undergoes significant antigenic variation. The HA stalk is more conserved, but this portion of the molecule is likely to be masked by the globular head and therefore not readily recognized receptors on antibody-producing B cells.

To make the HA stalk more accessible, an altered molecule was designed that lacks the globular head. To test whether this protein could give rise to broadly neutralizing antibodies, mice were immunized first with plasmid DNA encoding the truncated protein, and then with virus-like particles bearing the headless HA. When mice were immunized with headless HA from a 1934 H1N1 strain, all survived after intranasal challenge with the homologous virus. The sera from these mice showed broader reactivity against H2N2, H5N1, and 2009 pandemic H1N1 viruses than sera from mice immunized with full-length HA.

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