Phase I/II trial of a peptide-based COVID-19 T-cell activator in patients with B-cell deficiency
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Published:2023-08-18
Issue:1
Volume:14
Page:
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ISSN:2041-1723
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Container-title:Nature Communications
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language:en
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Short-container-title:Nat Commun
Author:
Heitmann Jonas S.ORCID, Tandler Claudia, Marconato Maddalena, Nelde AnnikaORCID, Habibzada Timorshah, Rittig Susanne M., Tegeler Christian M., Maringer YacineORCID, Jaeger Simon U., Denk Monika, Richter Marion, Oezbek Melek T., Wiesmüller Karl-Heinz, Bauer JensORCID, Rieth Jonas, Wacker MarcelORCID, Schroeder Sarah M.ORCID, Hoenisch Gravel NaomiORCID, Scheid JonasORCID, Märklin MelanieORCID, Henrich Annika, Klimovich Boris, Clar Kim L., Lutz Martina, Holzmayer Samuel, Hörber SebastianORCID, Peter Andreas, Meisner Christoph, Fischer Imma, Löffler Markus W.ORCID, Peuker Caroline Anna, Habringer StefanORCID, Goetze Thorsten O., Jäger Elke, Rammensee Hans-Georg, Salih Helmut R.ORCID, Walz Juliane S.ORCID
Abstract
AbstractT-cell immunity is central for control of COVID-19, particularly in patients incapable of mounting antibody responses. CoVac-1 is a peptide-based T-cell activator composed of SARS-CoV-2 epitopes with documented favorable safety profile and efficacy in terms of SARS-CoV-2-specific T-cell response. We here report a Phase I/II open-label trial (NCT04954469) in 54 patients with congenital or acquired B-cell deficiency receiving one subcutaneous CoVac-1 dose. Immunogenicity in terms of CoVac-1-induced T-cell responses and safety are the primary and secondary endpoints, respectively. No serious or grade 4 CoVac-1-related adverse events have been observed. Expected local granuloma formation has been observed in 94% of study subjects, whereas systemic reactogenicity has been mild or absent. SARS-CoV-2-specific T-cell responses have been induced in 86% of patients and are directed to multiple CoVac-1 peptides, not affected by any current Omicron variants and mediated by multifunctional T-helper 1 CD4+ T cells. CoVac-1-induced T-cell responses have exceeded those directed to the spike protein after mRNA-based vaccination of B-cell deficient patients and immunocompetent COVID-19 convalescents with and without seroconversion. Overall, our data show that CoVac-1 induces broad and potent T-cell responses in patients with B-cell/antibody deficiency with a favorable safety profile, which warrants advancement to pivotal Phase III safety and efficacy evaluation. ClinicalTrials.gov identifier NCT04954469.
Funder
Ministerium für Wissenschaft, Forschung und Kunst Baden-Württemberg Deutsche Forschungsgemeinschaft Deutsches Krebsforschungszentrum
Publisher
Springer Science and Business Media LLC
Subject
General Physics and Astronomy,General Biochemistry, Genetics and Molecular Biology,General Chemistry,Multidisciplinary
Reference48 articles.
1. Falsey, A. R. et al. Phase 3 Safety and Efficacy of AZD1222 (ChAdOx1 nCoV-19) Covid-19 Vaccine. N. Engl. J. Med. 385, 2348–2360 (2021). 2. Polack, F. P. et al. Safety and efficacy of the BNT162b2 mRNA Covid-19 vaccine. N. Engl. J. Med. 383, 2603–2615 (2020). 3. Baden, L. R. et al. Efficacy and safety of the mRNA-1273 SARS-CoV-2 vaccine. N. Engl. J. Med. 384, 403–416 (2021). 4. Heath, P. T. et al. Safety and efficacy of NVX-CoV2373 Covid-19 Vaccine. N. Engl. J. Med. 385, 1172–1183 (2021). 5. Herishanu, Y. et al. Efficacy of the BNT162b2 mRNA COVID-19 vaccine in patients with chronic lymphocytic leukemia. Blood 137, 3165–3173 (2021).
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