Induction of broad multifunctional CD8+ and CD4+ T cells by hepatitis B virus antigen-based synthetic long peptides ex vivo

Diahann T.S.L. Jansen, Monique T.A. de Beijer, Robbie J. Luijten, Kitty Kwappenberg, Anna Sophia Wiekmeijer, Amy L. Kessler, Roel F.A. Pieterman, Rachid Bouzid, Willem Jan Krebber, Robert A. de Man, Cornelis J.M. Melief, Sonja I. Buschow*

*Corresponding author for this work

Research output: Contribution to journalArticleAcademicpeer-review

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Therapeutic vaccination based on synthetic long peptides (SLP®) containing both CD4+ and CD8+ T cell epitopes is a promising treatment strategy for chronic hepatitis B infection (cHBV). 


We designed SLPs for three HBV proteins, HBcAg and the non-secreted proteins polymerase and X, and investigated their ability to induce T cell responses ex vivo. A set of 17 SLPs was constructed based on viral protein conservation, functionality, predicted and validated binders for prevalent human leukocyte antigen (HLA) supertypes, validated HLA I epitopes, and chemical producibility. 


All 17 SLPs were capable of inducing interferon gamma (IFNɣ) production in samples from four or more donors that had resolved an HBV infection in the past (resolver). Further analysis of the best performing SLPs demonstrated activation of both CD8+ and CD4+ multi-functional T cells in one or more resolver and patient sample(s). When investigating which SLP could activate HBV-specific T cells, the responses could be traced back to different peptides for each patient or resolver. 


This indicates that a large population of subjects with different HLA types can be covered by selecting a suitable mix of SLPs for therapeutic vaccine design. In conclusion, we designed a set of SLPs capable of inducing multifunctional CD8+ and CD4+ T cells ex vivo that create important components for a novel therapeutic vaccine to cure cHBV.

Original languageEnglish
Article number1163118
JournalFrontiers in Immunology
Publication statusPublished - 13 Sept 2023

Bibliographical note


This work was financed by the Dutch Ministry of Economic
Affairs and Climate Policy by means of the public–private
partnership (PPP) allowance from the Top Sector Life Sciences &
Health to stimulate public–private partnerships in conjunction with
the Dutch Digestive Foundation (LSHM16056). In the latter, ISA
Pharmaceuticals B.V. Leiden, the Netherlands, is the collaborating
and co-funding private partner.

Publisher Copyright:
Copyright © 2023 Jansen, de Beijer, Luijten, Kwappenberg, Wiekmeijer, Kessler, Pieterman, Bouzid, Krebber, de Man, Melief and Buschow.


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