Expansion of the HSV-2-specific T cell repertoire in skin after immunotherapeutic HSV-2 vaccine.

Autor:	Ford ES; Vaccine and Infectious Disease Division, Fred Hutch Cancer Center, Seattle, Washington, USA.; Division of Allergy and Infectious Diseases, Department of Medicine, and., Li AZ; Vaccine and Infectious Disease Division, Fred Hutch Cancer Center, Seattle, Washington, USA., Laing KJ; Division of Allergy and Infectious Diseases, Department of Medicine, and., Dong L; Division of Allergy and Infectious Diseases, Department of Medicine, and., Diem K; Department of Laboratory Medicine and Pathology, University of Washington, Seattle, Washington, USA., Jing L; Division of Allergy and Infectious Diseases, Department of Medicine, and., Mayer-Blackwell K; Vaccine and Infectious Disease Division, Fred Hutch Cancer Center, Seattle, Washington, USA., Basu K; Division of Allergy and Infectious Diseases, Department of Medicine, and., Ott M; Division of Allergy and Infectious Diseases, Department of Medicine, and., Tartaglia J; Sanofi, Swiftwater, Pennsylvania, USA., Gurunathan S; Sanofi, Swiftwater, Pennsylvania, USA., Reid JL; Translational Sciences and Therapeutics Division, Fred Hutch Cancer Center, Seattle, Washington, USA., Ecsedi M; Translational Sciences and Therapeutics Division, Fred Hutch Cancer Center, Seattle, Washington, USA., Chapuis AG; Translational Sciences and Therapeutics Division, Fred Hutch Cancer Center, Seattle, Washington, USA., Huang ML; Department of Laboratory Medicine and Pathology, University of Washington, Seattle, Washington, USA., Magaret AS; Vaccine and Infectious Disease Division, Fred Hutch Cancer Center, Seattle, Washington, USA.; Department of Laboratory Medicine and Pathology, University of Washington, Seattle, Washington, USA., Johnston C; Vaccine and Infectious Disease Division, Fred Hutch Cancer Center, Seattle, Washington, USA.; Division of Allergy and Infectious Diseases, Department of Medicine, and.; Department of Laboratory Medicine and Pathology, University of Washington, Seattle, Washington, USA., Zhu J; Vaccine and Infectious Disease Division, Fred Hutch Cancer Center, Seattle, Washington, USA.; Department of Laboratory Medicine and Pathology, University of Washington, Seattle, Washington, USA.; Institute of Stem Cell and Regenerative Medicine and., Koelle DM; Vaccine and Infectious Disease Division, Fred Hutch Cancer Center, Seattle, Washington, USA.; Division of Allergy and Infectious Diseases, Department of Medicine, and.; Department of Laboratory Medicine and Pathology, University of Washington, Seattle, Washington, USA.; Department of Global Health, University of Washington, Seattle, Washington, USA.; Benaroya Research Institute, Seattle, Washington, USA., Corey L; Vaccine and Infectious Disease Division, Fred Hutch Cancer Center, Seattle, Washington, USA.; Division of Allergy and Infectious Diseases, Department of Medicine, and.; Department of Laboratory Medicine and Pathology, University of Washington, Seattle, Washington, USA.
Jazyk:	angličtina
Zdroj:	JCI insight [JCI Insight] 2024 Jun 18; Vol. 9 (14). Date of Electronic Publication: 2024 Jun 18.
DOI:	10.1172/jci.insight.179010
Abstrakt:	The skin at the site of HSV-2 reactivation is enriched for HSV-2-specific T cells. To evaluate whether an immunotherapeutic vaccine could elicit skin-based memory T cells, we studied skin biopsies and HSV-2-reactive CD4+ T cells from PBMCs by T cell receptor (TCR) β chain (TRB) sequencing before and after vaccination with a replication-incompetent whole-virus HSV-2 vaccine candidate (HSV529). The representation of HSV-2-reactive CD4+ TRB sequences from PBMCs in the skin TRB repertoire increased after the first vaccine dose. We found sustained expansion after vaccination of unique, skin-based T cell clonotypes that were not detected in HSV-2-reactive CD4+ T cells isolated from PBMCs. In one participant, a switch in immunodominance occurred with the emergence of a TCR αβ pair after vaccination that was not detected in blood. This TCRαβ was shown to be HSV-2 reactive by expression of a synthetic TCR in a Jurkat-based NR4A1 reporter system. The skin in areas of HSV-2 reactivation possessed an oligoclonal TRB repertoire that was distinct from the circulation. Defining the influence of therapeutic vaccination on the HSV-2-specific TRB repertoire requires tissue-based evaluation.
Databáze:	MEDLINE
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