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Stephan, A.-S. ; Kosinska, A. ; Mück-Häusl, M. ; Muschaweckh, A.* ; Jager, C. ; Röder, N. ; Heikenwälder, M. ; Dembek, C.J. ; Protzer, U.

Evaluation of the effect of CD70 co-expression on CD8 T cell response in protein-prime MVA-boost vaccination in mice.

Vaccines 11:17 (2023)
Verlagsversion DOI PMC
Open Access Gold
Creative Commons Lizenzvertrag
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.
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Publikationstyp Artikel: Journalartikel
Dokumenttyp Wissenschaftlicher Artikel
Korrespondenzautor
Schlagwörter Cd70 ; Hepatitis B Virus ; Immune Therapy ; Vaccines; Chronic Hepatitis-b; Modified Vaccinia Virus; Human Dendritic Cells; Therapeutic Vaccination; Cd27/cd70 Pathway; Ifn-gamma; Cd27; Stimulation; Expression; Immunity
e-ISSN 2076-393X
Zeitschrift Vaccines
Quellenangaben Band: 11, Heft: 2, Seiten: , Artikelnummer: 17 Supplement: ,
Verlag MDPI
Verlagsort Basel
Nichtpatentliteratur Publikationen
Begutachtungsstatus Peer reviewed
Institut(e) Institute of Virology (VIRO)