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NIAID Scientists Advance Understanding of More Broadly Protective Flu Vaccines

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  • NIAID Scientists Advance Understanding of More Broadly Protective Flu Vaccines

    May 11, 2022
    NIAID Now

    In 1968, an influenza pandemic swept the globe, exposing everyone to a new flu strain and wiping out all traces of the H2N2 virus subtype, which had been responsible for the 1957 pandemic and had circulated for a decade afterward. People born after 1969 have thus never been exposed to H2 subtype influenza, while those born earlier have immunological experience with it. Researchers from the NIAID Vaccine Research Center (VRC) used this difference in immunological memory to investigate immune responses to a novel influenza vaccine candidate that VRC scientists had designed and developed. The vaccine candidate was tested in a Phase 1 trial led by VRC scientists Julie Ledgerwood, D.O., and Grace Chen, M.D. It was the first time this investigational vaccine had been tested in people. Results were published earlier this year in Nature Medicine.

    The trial vaccine is one of a still-experimental class of flu vaccines that could one day be used to provide long-lasting protection against multiple flu strains. ...

    ... In contrast to current flu vaccines, the vaccine candidate tested by the VRC scientists did not require growing live flu virus. Instead, the vaccine was produced in bioreactors and is based on ferritin, an iron-containing protein that spontaneously self-assembles into eight-sided nanoparticles. The nanoparticles serve as scaffolding to display multiple copies of HA protein arranged in a repetitive pattern that is very stimulating to the immune system. In the case of the ferritin nanoparticle vaccine tested in the recent trial, the HA protein displayed on the scaffold was from the now-extinct H2N2 flu subtype.

    In another difference from standard flu vaccines, the trial vaccine was designed to elicit antibodies not to the changeable head of HA but to its less variable “stem” portion. The stem of HA is shared across a wide range of flu subtypes and is thus an appealing target for the development of broadly protective flu vaccines. Clinical lots of the ferritin nanoparticle vaccine were manufactured by the Vaccine Clinical Materials Program at the Frederick National Laboratory. ...

    NIAID researchers designed a ferritin nanoparticle flu vaccine and tested it in people with and without immunological experience of the flu virus that caused the 1957 pandemic. The experimental vaccine prompted immune responses that suggested this kind of vaccine could provide long-lasting protection against many flu subtypes.
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