1区 · 综合性期刊
ArticleOA
作者: Fischer, Imma ; Peuker, Caroline Anna ; Klimovich, Boris ; Heitmann, Jonas S ; Denk, Monika ; Rammensee, Hans-Georg ; Jaeger, Simon U ; Lutz, Martina ; Clar, Kim L ; Habringer, Stefan ; Bauer, Jens ; Jäger, Elke ; Wacker, Marcel ; Rittig, Susanne M ; Löffler, Markus W ; Holzmayer, Samuel ; Habibzada, Timorshah ; Salih, Helmut R ; Hörber, Sebastian ; Oezbek, Melek T ; Tegeler, Christian M ; Marconato, Maddalena ; Peter, Andreas ; Scheid, Jonas ; Hoenisch Gravel, Naomi ; Märklin, Melanie ; Richter, Marion ; Henrich, Annika ; Schroeder, Sarah M ; Tandler, Claudia ; Nelde, Annika ; Maringer, Yacine ; Goetze, Thorsten O ; Walz, Juliane S ; Meisner, Christoph ; Wiesmüller, Karl-Heinz ; Rieth, Jonas
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.
