HLA I immunopeptidome of synthetic long peptide pulsed human dendritic cells for therapeutic vaccine design

Amy L. Kessler; Roel F.A. Pieterman; Wouter A.S. Doff; Karel Bezstarosti; Rachid Bouzid; Kim Klarenaar; Diahann T.S.L. Jansen; Robbie J. Luijten; Jeroen A.A. Demmers; Sonja I. Buschow

doi:10.1038/s41541-025-01069-1

HLA I immunopeptidome of synthetic long peptide pulsed human dendritic cells for therapeutic vaccine design

Amy L. Kessler, Roel F.A. Pieterman, Wouter A.S. Doff, Karel Bezstarosti, Rachid Bouzid, Kim Klarenaar, Diahann T.S.L. Jansen, Robbie J. Luijten, Jeroen A.A. Demmers, Sonja I. Buschow^*

^*Corresponding author for this work

Research output: Contribution to journal › Article › Academic › peer-review

Abstract

Synthetic long peptides (SLPs) are a promising vaccine modality that exploit dendritic cells (DC) to treat chronic infections or cancer. Currently, the design of SLPs relies on in silico prediction and multifactorial T cells assays to determine which SLPs are best cross-presented on DC human leukocyte antigen class I (HLA-I). Furthermore, it is unknown how TLR ligand-based adjuvants affect DC cross-presentation. Here, we generated a unique, high-quality immunopeptidome dataset of human DCs pulsed with 12 hepatitis B virus (HBV)-based SLPs combined with either a TLR1/2 (Amplivant®) or TLR3 (PolyI:C) ligand. The obtained immunopeptidome reflected adjuvant-induced differences, but no differences in cross-presentation of SLPs. We uncovered dominant (cross-)presentation on B-alleles, and identified 33 unique SLP-derived HLA-I peptides, several of which were not in silico predicted and some were consistently found across donors. Our work puts forward DC immunopeptidomics as a valuable tool for therapeutic vaccine design.

Original language	English
Article number	12
Journal	npj Vaccines
Volume	10
Issue number	1
DOIs	https://doi.org/10.1038/s41541-025-01069-1
Publication status	Published - 18 Jan 2025
Externally published	Yes

Bibliographical note

Publisher Copyright:
© The Author(s) 2025.

Funding

We would like to thank Prof. Dr. C.J.M. Melief for critical reading of the manuscript. 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, was the collaborating and co-funding private partner.

Funders	Funder number
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 (LSHM160
Dutch Ministry of Economic Affairs and Climate Policy	LSHM16056
Dutch Digestive Foundation
ISA Pharmaceuticals B.V. Leiden, The Netherlands

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This output contributes to the following UN Sustainable Development Goals (SDGs)

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title = "HLA I immunopeptidome of synthetic long peptide pulsed human dendritic cells for therapeutic vaccine design",

abstract = "Synthetic long peptides (SLPs) are a promising vaccine modality that exploit dendritic cells (DC) to treat chronic infections or cancer. Currently, the design of SLPs relies on in silico prediction and multifactorial T cells assays to determine which SLPs are best cross-presented on DC human leukocyte antigen class I (HLA-I). Furthermore, it is unknown how TLR ligand-based adjuvants affect DC cross-presentation. Here, we generated a unique, high-quality immunopeptidome dataset of human DCs pulsed with 12 hepatitis B virus (HBV)-based SLPs combined with either a TLR1/2 (Amplivant{\textregistered}) or TLR3 (PolyI:C) ligand. The obtained immunopeptidome reflected adjuvant-induced differences, but no differences in cross-presentation of SLPs. We uncovered dominant (cross-)presentation on B-alleles, and identified 33 unique SLP-derived HLA-I peptides, several of which were not in silico predicted and some were consistently found across donors. Our work puts forward DC immunopeptidomics as a valuable tool for therapeutic vaccine design.",

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doi = "10.1038/s41541-025-01069-1",

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AU - Kessler, Amy L.

AU - Pieterman, Roel F.A.

AU - Doff, Wouter A.S.

AU - Bezstarosti, Karel

AU - Bouzid, Rachid

AU - Klarenaar, Kim

AU - Jansen, Diahann T.S.L.

AU - Luijten, Robbie J.

AU - Demmers, Jeroen A.A.

AU - Buschow, Sonja I.

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N2 - Synthetic long peptides (SLPs) are a promising vaccine modality that exploit dendritic cells (DC) to treat chronic infections or cancer. Currently, the design of SLPs relies on in silico prediction and multifactorial T cells assays to determine which SLPs are best cross-presented on DC human leukocyte antigen class I (HLA-I). Furthermore, it is unknown how TLR ligand-based adjuvants affect DC cross-presentation. Here, we generated a unique, high-quality immunopeptidome dataset of human DCs pulsed with 12 hepatitis B virus (HBV)-based SLPs combined with either a TLR1/2 (Amplivant®) or TLR3 (PolyI:C) ligand. The obtained immunopeptidome reflected adjuvant-induced differences, but no differences in cross-presentation of SLPs. We uncovered dominant (cross-)presentation on B-alleles, and identified 33 unique SLP-derived HLA-I peptides, several of which were not in silico predicted and some were consistently found across donors. Our work puts forward DC immunopeptidomics as a valuable tool for therapeutic vaccine design.

AB - Synthetic long peptides (SLPs) are a promising vaccine modality that exploit dendritic cells (DC) to treat chronic infections or cancer. Currently, the design of SLPs relies on in silico prediction and multifactorial T cells assays to determine which SLPs are best cross-presented on DC human leukocyte antigen class I (HLA-I). Furthermore, it is unknown how TLR ligand-based adjuvants affect DC cross-presentation. Here, we generated a unique, high-quality immunopeptidome dataset of human DCs pulsed with 12 hepatitis B virus (HBV)-based SLPs combined with either a TLR1/2 (Amplivant®) or TLR3 (PolyI:C) ligand. The obtained immunopeptidome reflected adjuvant-induced differences, but no differences in cross-presentation of SLPs. We uncovered dominant (cross-)presentation on B-alleles, and identified 33 unique SLP-derived HLA-I peptides, several of which were not in silico predicted and some were consistently found across donors. Our work puts forward DC immunopeptidomics as a valuable tool for therapeutic vaccine design.

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HLA I immunopeptidome of synthetic long peptide pulsed human dendritic cells for therapeutic vaccine design

Abstract

Bibliographical note

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