Department of Biochemistry and Molecular Pharmacology; Schiffer Lab
Biochemistry | Immunoprophylaxis and Therapy | Medicinal Chemistry and Pharmaceutics | Medicinal-Pharmaceutical Chemistry | Molecular Biology | Structural Biology | Virus Diseases
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 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.
H7N9, T cell, T cell epitope, epitope prediction, hemagglutinin, immunoinformatics, influenza, molecular modeling, pandemic, structure-based vaccine design, vaccine
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Copyright © 2018 The Author(s). This is an Open Access article distributed under the terms of the Creative Commons Attribution-NonCommercial-NoDerivatives License (http://creativecommons.org/licenses/by-nc-nd/4.0/), which permits non-commercial re-use, distribution, and reproduction in any medium, provided the original work is properly cited, and is not altered, transformed, or built upon in any way.
DOI of Published Version
Hum Vaccin Immunother. 2018;14(9):2203-2207. doi: 10.1080/21645515.2018.1495303. Epub 2018 Sep 5. Link to article on publisher's site
Human vaccines and immunotherapeutics
Moise, Leonard; Biron, Bethany M.; Boyle, Christine M.; Yilmaz, Nese Kurt; Jang, Hyesun; Schiffer, Celia A.; Ross, Ted M.; Martin, William D.; and De Groot, Anne S., "T cell epitope engineering: an avian H7N9 influenza vaccine strategy for pandemic preparedness and response" (2018). Schiffer Lab Publications. 24.
Creative Commons License
This work is licensed under a Creative Commons Attribution-Noncommercial-No Derivative Works 4.0 License.
Biochemistry Commons, Immunoprophylaxis and Therapy Commons, Medicinal Chemistry and Pharmaceutics Commons, Medicinal-Pharmaceutical Chemistry Commons, Molecular Biology Commons, Structural Biology Commons, Virus Diseases Commons