Preprint Article Version 1 Preserved in Portico This version is not peer-reviewed

Preferential Expansion of HPV16 E1-Specific T Cells from Healthy Donors’ PBMCs after Ex Vivo Immunization with an E1E2E6E7 Fusion Antigen

Joana Daradoumis
* ORCID logo ,
Mikkel Dons Müller
ORCID logo ,
Patrick Neckermann
,
Benedikt Asbach
ORCID logo ,
Silke Schrödel
,
Christian Thirion
,
Ralf Wagner
,
Per Thor Straten
,
Peter Johannes Holst
,
Ditte Boilesen
*
Version 1 : Received: 2 November 2023 / Approved: 3 November 2023 / Online: 3 November 2023 (10:08:20 CET)

A peer-reviewed article of this Preprint also exists.

Daradoumis, J.; Müller, M.D.; Neckermann, P.; Asbach, B.; Schrödel, S.; Thirion, C.; Wagner, R.; thor Straten, P.; Holst, P.J.; Boilesen, D. Preferential Expansion of HPV16 E1-Specific T Cells from Healthy Donors’ PBMCs after Ex Vivo Immunization with an E1E2E6E7 Fusion Antigen. Cancers 2023, 15, 5863. Daradoumis, J.; Müller, M.D.; Neckermann, P.; Asbach, B.; Schrödel, S.; Thirion, C.; Wagner, R.; thor Straten, P.; Holst, P.J.; Boilesen, D. Preferential Expansion of HPV16 E1-Specific T Cells from Healthy Donors’ PBMCs after Ex Vivo Immunization with an E1E2E6E7 Fusion Antigen. Cancers 2023, 15, 5863.

Abstract

Persistent human papillomavirus (HPV) infection is responsible for practically all cervical and a high proportion of anogenital and oropharyngeal cancers. Therapeutic HPV vaccines in clinical development show great promise in improving outcomes for patients who mount an anti-HPV T cell response, but far from all patients elicit a sufficient immunological response. This witnesses a translational gap between animal models and human patients. Here, we investigated the potential of a new assay consisting of co-culturing vaccine-transduced dendritic cells (DCs) with syngeneic healthy human peripheral blood mononuclear cells (PBMCs) to mimic a human in vivo immunization. This new promising human ex vivo PBMC assay was evaluated using an innovative therapeutic adenovirus (Adv)-based HPV vaccine encoding the E1, E2, E6, and E7 HPV16 genes. This new method allowed us to show that vaccine-transduced DCs yielded functional effector T cells and unveiled information on immunohierarchy showing E1-specific T cell immunodominance over time. We suggest that this assay can be a valuable translational tool to complement the known animal models, not only for HPV therapeutic vaccines, and supports the use of E1 as an immunotherapeutic target. Nevertheless, the findings reported here need to be validated in a larger number of donors, and preferably in patient samples.

Keywords

human papillomavirus; adenoviral vectors; adenovirus-vector-based vaccines; therapeutic vaccines; E1 HPV16; T cell expansion

Subject

Biology and Life Sciences, Immunology and Microbiology

Copyright: This is an open access article distributed under the Creative Commons Attribution License which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

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