Research & Innovation
Publications
Phase I/II trial of a peptide-based COVID-19 T-cell activator in patients with B-cell deficiency
PMU Author
Simon U Jaeger
All Authors
Jonas S Heitmann, Claudia Tandler, Maddalena Marconato, Annika Nelde, Timorshah Habibzada, Susanne M Rittig, Christian M Tegeler, Yacine Maringer, Simon U Jaeger, Monika Denk, Marion Richter, Melek T Oezbek, Karl-Heinz Wiesmüller, Jens Bauer, Jonas Rieth, Marcel Wacker, Sarah M Schroeder, Naomi Hoenisch Gravel, Jonas Scheid, Melanie Märklin, Annika Henrich, Boris Klimovich, Kim L Clar, Martina Lutz, Samuel Holzmayer, Sebastian Hörber, Andreas Peter, Christoph Meisner, Imma Fischer, Markus W Löffler, Caroline Anna Peuker, Stefan Habringer, Thorsten O Goetze, Elke Jäger, Hans-Georg Rammensee, Helmut R Salih, Juliane S Walz
Journal association
Nature Communications
Abstract
T-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.
Keywords
Humans, COVID-19, SARS-CoV-2, T-Lymphocytes, Agammaglobulinemia, Peptides/therapeutic use