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Xu Z, Chokkalingam N, Tello-Ruiz E, et al. Incorporation of a Novel CD4+ Helper Epitope Identified from Aquifex aeolicus Enhances Humoral Responses Induced by DNA and Protein Vaccinations. iScience. 2020;23(8):101399doi: 10.1016/j.isci.2020.101399.
Xu, Z., Chokkalingam, N., Tello-Ruiz, E., Walker, S., Kulp, D. W., & Weiner, D. B. (2020). Incorporation of a Novel CD4+ Helper Epitope Identified from Aquifex aeolicus Enhances Humoral Responses Induced by DNA and Protein Vaccinations. iScience, 23(8), 101399. https://doi.org/10.1016/j.isci.2020.101399
Xu, Ziyang, et al. "Incorporation of a Novel CD4+ Helper Epitope Identified from Aquifex aeolicus Enhances Humoral Responses Induced by DNA and Protein Vaccinations." iScience vol. 23,8 (2020): 101399. doi: https://doi.org/10.1016/j.isci.2020.101399
Xu Z, Chokkalingam N, Tello-Ruiz E, Walker S, Kulp DW, Weiner DB. Incorporation of a Novel CD4+ Helper Epitope Identified from Aquifex aeolicus Enhances Humoral Responses Induced by DNA and Protein Vaccinations. iScience. 2020 Aug 21;23(8):101399. doi: 10.1016/j.isci.2020.101399. Epub 2020 Aug 06. PMID: 32763137; PMCID: PMC7409978.
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iScience. 2020 Aug 21;23(8):101399. doi: 10.1016/j.isci.2020.101399. Epub 2020 Aug 06.

Incorporation of a Novel CD4+ Helper Epitope Identified from Aquifex aeolicus Enhances Humoral Responses Induced by DNA and Protein Vaccinations.

iScience

Ziyang Xu, Neethu Chokkalingam, Edgar Tello-Ruiz, Susanne Walker, Daniel W Kulp, David B Weiner

Affiliations

  1. The Vaccine and Immunotherapy Center, Wistar Institute, Philadelphia, PA 19104, USA; Department of Pharmacology, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA 19104, USA.
  2. The Vaccine and Immunotherapy Center, Wistar Institute, Philadelphia, PA 19104, USA.
  3. The Vaccine and Immunotherapy Center, Wistar Institute, Philadelphia, PA 19104, USA. Electronic address: [email protected].
  4. The Vaccine and Immunotherapy Center, Wistar Institute, Philadelphia, PA 19104, USA. Electronic address: [email protected].

PMID: 32763137 PMCID: PMC7409978 DOI: 10.1016/j.isci.2020.101399

Abstract

CD4+ T cells play an important role in the maturation of the antibody responses. Conjugation of identified CD4+ T cell helper epitope to the target antigen has been developed as a strategy to enhance vaccine-induced humoral immunity. In this work, we reported the identification of a novel HLA-IAb helper epitope LS-3 from Aquifex aeolicus. In silico analysis predicted this epitope to have high binding affinity to common human HLA alleles and have complementary binding coverage to the established PADRE epitope. Introduction of HLA-IAb knockout mutations to the LS-3 epitope significantly attenuated humoral responses induced by a vaccine containing this epitope. Finally, engineered fusion of the epitope to a model antigen, influenza hemagglutinin, significantly improved both binding and hemagglutination inhibition antibody responses in mice receiving DNA or protein vaccines. In summary, LS-3 and additional identified CD4+ helper epitopes may be further explored to improve vaccine responses in translational studies.

Copyright © 2020 The Authors. Published by Elsevier Inc. All rights reserved.

Keywords: Cell Biology; Immunology

Conflict of interest statement

Declaration of Interests Z.X., D.W.K., and D.B.W. have a pending US patent on genetic fusion constructs with the identified LS-3 epitope. D.B.W. has received grant funding, participates in industry co

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