A COVID-19 peptide vaccine for the induction of SARS-CoV-2 T cell immunity.

Autor: Heitmann JS; Clinical Collaboration Unit Translational Immunology, German Cancer Consortium (DKTK), Department of Internal Medicine, University Hospital Tübingen, Tübingen, Germany.; Cluster of Excellence iFIT (EXC2180) 'Image-Guided and Functionally Instructed Tumor Therapies', University of Tübingen, Tübingen, Germany., Bilich T; Clinical Collaboration Unit Translational Immunology, German Cancer Consortium (DKTK), Department of Internal Medicine, University Hospital Tübingen, Tübingen, Germany.; Cluster of Excellence iFIT (EXC2180) 'Image-Guided and Functionally Instructed Tumor Therapies', University of Tübingen, Tübingen, Germany.; Institute for Cell Biology, Department of Immunology, University of Tübingen, Tübingen, Germany., Tandler C; Clinical Collaboration Unit Translational Immunology, German Cancer Consortium (DKTK), Department of Internal Medicine, University Hospital Tübingen, Tübingen, Germany.; Cluster of Excellence iFIT (EXC2180) 'Image-Guided and Functionally Instructed Tumor Therapies', University of Tübingen, Tübingen, Germany.; Institute for Cell Biology, Department of Immunology, University of Tübingen, Tübingen, Germany., Nelde A; Clinical Collaboration Unit Translational Immunology, German Cancer Consortium (DKTK), Department of Internal Medicine, University Hospital Tübingen, Tübingen, Germany.; Cluster of Excellence iFIT (EXC2180) 'Image-Guided and Functionally Instructed Tumor Therapies', University of Tübingen, Tübingen, Germany.; Institute for Cell Biology, Department of Immunology, University of Tübingen, Tübingen, Germany., Maringer Y; Clinical Collaboration Unit Translational Immunology, German Cancer Consortium (DKTK), Department of Internal Medicine, University Hospital Tübingen, Tübingen, Germany.; Cluster of Excellence iFIT (EXC2180) 'Image-Guided and Functionally Instructed Tumor Therapies', University of Tübingen, Tübingen, Germany.; Institute for Cell Biology, Department of Immunology, University of Tübingen, Tübingen, Germany., Marconato M; Clinical Collaboration Unit Translational Immunology, German Cancer Consortium (DKTK), Department of Internal Medicine, University Hospital Tübingen, Tübingen, Germany., Reusch J; Clinical Collaboration Unit Translational Immunology, German Cancer Consortium (DKTK), Department of Internal Medicine, University Hospital Tübingen, Tübingen, Germany., Jäger S; Clinical Collaboration Unit Translational Immunology, German Cancer Consortium (DKTK), Department of Internal Medicine, University Hospital Tübingen, Tübingen, Germany.; Dr. Margarete Fischer-Bosch Institute of Clinical Pharmacology, Stuttgart, Germany.; Department of Clinical Pharmacology, University Hospital Tübingen, Tübingen, Germany., Denk M; Institute for Cell Biology, Department of Immunology, University of Tübingen, Tübingen, Germany., Richter M; Institute for Cell Biology, Department of Immunology, University of Tübingen, Tübingen, Germany., Anton L; Clinical Collaboration Unit Translational Immunology, German Cancer Consortium (DKTK), Department of Internal Medicine, University Hospital Tübingen, Tübingen, Germany., Weber LM; Clinical Collaboration Unit Translational Immunology, German Cancer Consortium (DKTK), Department of Internal Medicine, University Hospital Tübingen, Tübingen, Germany., Roerden M; Cluster of Excellence iFIT (EXC2180) 'Image-Guided and Functionally Instructed Tumor Therapies', University of Tübingen, Tübingen, Germany.; Institute for Cell Biology, Department of Immunology, University of Tübingen, Tübingen, Germany.; Department of Hematology, Oncology, Clinical Immunology and Rheumatology, University Hospital Tübingen, Tübingen, Germany., Bauer J; Clinical Collaboration Unit Translational Immunology, German Cancer Consortium (DKTK), Department of Internal Medicine, University Hospital Tübingen, Tübingen, Germany.; Cluster of Excellence iFIT (EXC2180) 'Image-Guided and Functionally Instructed Tumor Therapies', University of Tübingen, Tübingen, Germany.; Institute for Cell Biology, Department of Immunology, University of Tübingen, Tübingen, Germany., Rieth J; Clinical Collaboration Unit Translational Immunology, German Cancer Consortium (DKTK), Department of Internal Medicine, University Hospital Tübingen, Tübingen, Germany.; Institute for Cell Biology, Department of Immunology, University of Tübingen, Tübingen, Germany., Wacker M; Clinical Collaboration Unit Translational Immunology, German Cancer Consortium (DKTK), Department of Internal Medicine, University Hospital Tübingen, Tübingen, Germany.; Cluster of Excellence iFIT (EXC2180) 'Image-Guided and Functionally Instructed Tumor Therapies', University of Tübingen, Tübingen, Germany.; Institute for Cell Biology, Department of Immunology, University of Tübingen, Tübingen, Germany., Hörber S; Institute for Clinical Chemistry and Pathobiochemistry, Department for Diagnostic Laboratory Medicine, University Hospital Tübingen, Tübingen, Germany., Peter A; Institute for Clinical Chemistry and Pathobiochemistry, Department for Diagnostic Laboratory Medicine, University Hospital Tübingen, Tübingen, Germany., Meisner C; Institute for Clinical Epidemiology and Applied Biometry, University Hospital Tübingen, Tübingen, Germany.; Robert Bosch Hospital, Robert Bosch Society for Medical Research, Stuttgart, Germany., Fischer I; Institute for Clinical Epidemiology and Applied Biometry, University Hospital Tübingen, Tübingen, Germany., Löffler MW; Cluster of Excellence iFIT (EXC2180) 'Image-Guided and Functionally Instructed Tumor Therapies', University of Tübingen, Tübingen, Germany.; Institute for Cell Biology, Department of Immunology, University of Tübingen, Tübingen, Germany.; Department of Clinical Pharmacology, University Hospital Tübingen, Tübingen, Germany.; German Cancer Consortium (DKTK) and German Cancer Research Center (DKFZ), partner site Tübingen, Tübingen, Germany.; Department of General, Visceral and Transplant Surgery, University Hospital Tübingen, Tübingen, Germany., Karbach J; Department of Oncology and Hematology, Krankenhaus Nordwest, Frankfurt, Germany., Jäger E; Department of Oncology and Hematology, Krankenhaus Nordwest, Frankfurt, Germany., Klein R; Department of Hematology, Oncology, Clinical Immunology and Rheumatology, University Hospital Tübingen, Tübingen, Germany., Rammensee HG; Cluster of Excellence iFIT (EXC2180) 'Image-Guided and Functionally Instructed Tumor Therapies', University of Tübingen, Tübingen, Germany.; Institute for Cell Biology, Department of Immunology, University of Tübingen, Tübingen, Germany.; German Cancer Consortium (DKTK) and German Cancer Research Center (DKFZ), partner site Tübingen, Tübingen, Germany., Salih HR; Clinical Collaboration Unit Translational Immunology, German Cancer Consortium (DKTK), Department of Internal Medicine, University Hospital Tübingen, Tübingen, Germany.; Cluster of Excellence iFIT (EXC2180) 'Image-Guided and Functionally Instructed Tumor Therapies', University of Tübingen, Tübingen, Germany., Walz JS; Clinical Collaboration Unit Translational Immunology, German Cancer Consortium (DKTK), Department of Internal Medicine, University Hospital Tübingen, Tübingen, Germany. juliane.walz@med.uni-tuebingen.de.; Cluster of Excellence iFIT (EXC2180) 'Image-Guided and Functionally Instructed Tumor Therapies', University of Tübingen, Tübingen, Germany. juliane.walz@med.uni-tuebingen.de.; Institute for Cell Biology, Department of Immunology, University of Tübingen, Tübingen, Germany. juliane.walz@med.uni-tuebingen.de.; Dr. Margarete Fischer-Bosch Institute of Clinical Pharmacology, Stuttgart, Germany. juliane.walz@med.uni-tuebingen.de.; Robert Bosch Center for Tumor Diseases (RBCT), Stuttgart, Germany. juliane.walz@med.uni-tuebingen.de.
Jazyk: angličtina
Zdroj: Nature [Nature] 2022 Jan; Vol. 601 (7894), pp. 617-622. Date of Electronic Publication: 2021 Nov 23.
DOI: 10.1038/s41586-021-04232-5
Abstrakt: T cell immunity is central for the control of viral infections. CoVac-1 is a peptide-based vaccine candidate, composed of SARS-CoV-2 T cell epitopes derived from various viral proteins 1,2 , combined with the Toll-like receptor 1/2 agonist XS15 emulsified in Montanide ISA51 VG, aiming to induce profound SARS-CoV-2 T cell immunity to combat COVID-19. Here we conducted a phase I open-label trial, recruiting 36 participants aged 18-80 years, who received a single subcutaneous CoVac-1 vaccination. The primary end point was safety analysed until day 56. Immunogenicity in terms of CoVac-1-induced T cell response was analysed as the main secondary end point until day 28 and in the follow-up until month 3. No serious adverse events and no grade 4 adverse events were observed. Expected local granuloma formation was observed in all study participants, whereas systemic reactogenicity was absent or mild. SARS-CoV-2-specific T cell responses targeting multiple vaccine peptides were induced in all study participants, mediated by multifunctional T helper 1 CD4 + and CD8 + T cells. CoVac-1-induced IFNγ T cell responses persisted in the follow-up analyses and surpassed those detected after SARS-CoV-2 infection as well as after vaccination with approved vaccines. Furthermore, vaccine-induced T cell responses were unaffected by current SARS-CoV-2 variants of concern. Together, CoVac-1 showed a favourable safety profile and induced broad, potent and variant of concern-independent T cell responses, supporting the presently ongoing evaluation in a phase II trial for patients with B cell or antibody deficiency.
(© 2022. The Author(s).)
Databáze: MEDLINE
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