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T cell epitope engineering: an avian H7N9 influenza vaccine strategy for pandemic preparedness and response

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  • T cell epitope engineering: an avian H7N9 influenza vaccine strategy for pandemic preparedness and response

    Hum Vaccin Immunother. 2018 Jul 17. doi: 10.1080/21645515.2018.1495303. [Epub ahead of print]
    T cell epitope engineering: an avian H7N9 influenza vaccine strategy for pandemic preparedness and response.

    Moise L1,2,3, Girard B1, Boyle C1, Kurt Yilmaz N4, Jang H5, Schiffer C4, Ross T5,6, Martin WD1, De Groot AS1,2,3.
    Author information

    Abstract

    The delayed availability of vaccine during the 2009 H1N1 influenza pandemic created a sense of urgency to better prepare for the next influenza pandemic. Advancements in manufacturing technology, speed and capacity have been achieved but vaccine effectiveness remains a significant challenge. Here, we describe a novel vaccine design strategy called immune engineering in the context of H7N9 influenza vaccine development. The approach combines immunoinformatic and structure modeling methods to promote protective antibody responses against H7N9 hemagglutinin (HA) by engineering whole antigens to carry seasonal influenza HA memory CD4+ T cell epitopes - without perturbing native antigen structure - by galvanizing HA-specific memory helper T cells that support sustained antibody development against the native target HA. The premise for this vaccine concept rests on (i) the significance of CD4+ T cell memory to influenza immunity, (ii) the essential role CD4+ T cells play in development of neutralizing antibodies, (iii) linked specificity of hemagglutinin (HA)-derived CD4+ T cell epitopes to antibody responses, (iv) the structural plasticity of HA and (v) an illustration of improved antibody response to a prototype engineered recombinant H7-HA vaccine. Immune engineering can be applied to development of vaccines against pandemic concerns, including avian influenza, as well as other difficult targets.


    PMID: 30015562 DOI: 10.1080/21645515.2018.1495303
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