Evaluation of the Effect of CD70 Co-Expression on CD8 T Cell Response in Protein-Prime MVA-Boost Vaccination in Mice

Stephan, Ann-Sophie; Kosinska, Anna D.; Mück-Häusl, Martin; Muschaweckh, Andreas; Jäger, Clemens; Röder, Natalie; Heikenwälder, Mathias; Dembek, Claudia; Protzer, Ulrike

doi:10.3390/vaccines11020245

Open AccessArticle

Evaluation of the Effect of CD70 Co-Expression on CD8 T Cell Response in Protein-Prime MVA-Boost Vaccination in Mice

by

Ann-Sophie Stephan

^1,†,

Anna D. Kosinska

^1,2,†,

Martin Mück-Häusl

^1,‡,

Andreas Muschaweckh

³

,

Clemens Jäger

¹,

Natalie Röder

¹,

Mathias Heikenwälder

^1,4,

Claudia Dembek

^1,2,*,† and

Ulrike Protzer

^1,2,*,†

¹

Institute of Virology, Technical University of Munich, Helmholtz Zentrum München, 81675 Munich, Germany

²

German Center for Infection Research (DZIF), Partner Site Munich, 81675 Munich, Germany

³

Institute for Experimental Neuroimmunology, Technical University of Munich School of Medicine, 81675 Munich, Germany

⁴

Division of Chronic Inflammation and Cancer, German Cancer Research Center (DKFZ) Heidelberg, 69120 Heidelberg, Germany

^*

Authors to whom correspondence should be addressed.

^†

These authors contributed equally to this work.

^‡

Current address: Institute of Regenerative Biology and Medicine, Helmholtz Zentrum München, 85764 Munich, Germany.

Vaccines 2023, 11(2), 245; https://doi.org/10.3390/vaccines11020245

Submission received: 4 December 2022 / Revised: 14 January 2023 / Accepted: 17 January 2023 / Published: 21 January 2023

Download

Browse Figures

Versions Notes

Abstract

Here, we investigate the potential of CD70 co-expression during viral vector boost vaccination to improve an antigen-specific T cell response. To determine the chance of activating antigen-specific T cells by CD70, we used the HBV core antigen as a model antigen in a heterologous protein-prime, Modified Vaccinia virus Ankara (MVA) boost vaccination scheme. Both the HBV core and a CD70 expression cassette were co-expressed upon delivery by an MVA vector under the same promoter linked by a P2A site. To compare immunogenicity with and without CD70 co-expression, HBV-naïve, C57BL/6 (wt) mice and HBV-transgenic mice were prime-vaccinated using recombinant HBV core antigen followed by the MVA vector boost. Co-expression of CD70 increased the number of vaccine-induced HBV core-specific CD8 T cells by >2-fold and improved their effector functions in HBV-naïve mice. In vaccinated HBV1.3tg mice, the number and functionality of HBV core-specific CD8 T cells was slightly increased upon CD70 co-expression in low-viremic, but not in high-viremic animals. CD70 co-expression did not impact liver damage as indicated by ALT levels in the serum, but increased the number of vaccine-induced, proliferative T cell clusters in the liver. Overall, this study indicates that orchestrated co-expression of CD70 and a vaccine antigen may be an interesting and safe means of enhancing antigen-specific CD8 T cell responses using vector-based vaccines, although in our study it was not sufficient to break immune tolerance.

Keywords: hepatitis B virus; vaccines; immune therapy; CD70

Share and Cite

MDPI and ACS Style

Stephan, A.-S.; Kosinska, A.D.; Mück-Häusl, M.; Muschaweckh, A.; Jäger, C.; Röder, N.; Heikenwälder, M.; Dembek, C.; Protzer, U. Evaluation of the Effect of CD70 Co-Expression on CD8 T Cell Response in Protein-Prime MVA-Boost Vaccination in Mice. Vaccines 2023, 11, 245. https://doi.org/10.3390/vaccines11020245

AMA Style

Stephan A-S, Kosinska AD, Mück-Häusl M, Muschaweckh A, Jäger C, Röder N, Heikenwälder M, Dembek C, Protzer U. Evaluation of the Effect of CD70 Co-Expression on CD8 T Cell Response in Protein-Prime MVA-Boost Vaccination in Mice. Vaccines. 2023; 11(2):245. https://doi.org/10.3390/vaccines11020245

Chicago/Turabian Style

Stephan, Ann-Sophie, Anna D. Kosinska, Martin Mück-Häusl, Andreas Muschaweckh, Clemens Jäger, Natalie Röder, Mathias Heikenwälder, Claudia Dembek, and Ulrike Protzer. 2023. "Evaluation of the Effect of CD70 Co-Expression on CD8 T Cell Response in Protein-Prime MVA-Boost Vaccination in Mice" Vaccines 11, no. 2: 245. https://doi.org/10.3390/vaccines11020245

APA Style

Stephan, A.-S., Kosinska, A. D., Mück-Häusl, M., Muschaweckh, A., Jäger, C., Röder, N., Heikenwälder, M., Dembek, C., & Protzer, U. (2023). Evaluation of the Effect of CD70 Co-Expression on CD8 T Cell Response in Protein-Prime MVA-Boost Vaccination in Mice. Vaccines, 11(2), 245. https://doi.org/10.3390/vaccines11020245

Note that from the first issue of 2016, this journal uses article numbers instead of page numbers. See further details here.

Article Menu

Evaluation of the Effect of CD70 Co-Expression on CD8 T Cell Response in Protein-Prime MVA-Boost Vaccination in Mice

Abstract

Share and Cite

Article Metrics

Article Access Statistics

Further Information

Guidelines

MDPI Initiatives

Follow MDPI