UMMS Affiliation

Department of Biochemistry and Molecular Pharmacology; Schiffer Lab

Publication Date

2018-09-05

Document Type

Article

Disciplines

Biochemistry | Immunoprophylaxis and Therapy | Medicinal Chemistry and Pharmaceutics | Medicinal-Pharmaceutical Chemistry | Molecular Biology | Structural Biology | Virus Diseases

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 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.

Keywords

H7N9, T cell, T cell epitope, epitope prediction, hemagglutinin, immunoinformatics, influenza, molecular modeling, pandemic, structure-based vaccine design, vaccine

Rights and Permissions

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

10.1080/21645515.2018.1495303

Source

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

Journal/Book/Conference Title

Human vaccines and immunotherapeutics

Related Resources

Link to Article in PubMed

PubMed ID

30015562

Creative Commons License

Creative Commons Attribution-Noncommercial-No Derivative Works 4.0 License
This work is licensed under a Creative Commons Attribution-Noncommercial-No Derivative Works 4.0 License.

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