Abstract CT258: Interim safety and immunogenicity results of a phase I trial evaluating the multi-peptide COVID-19 vaccine candidate CoVac-1 for induction of SARS-CoV-2 T cell immunity in cancer patients with disease- or treatment-related immunoglobulin deficiency

Abstract Individuals with impaired ability to mount a humoral immune response, either during natural infection or upon prophylactic vaccination, are at high risk for a severe course of COVID-19. Besides humoral immunity mediated by B cells, T cell immunity is key for the control of viral infections. We developed the peptide-based vaccine candidate CoVac-1, which primarily aims for the induction of SARS-CoV-2-specific T cells. CoVac-1 comprises six promiscuous HLA-DR-binding SARS-CoV-2-derived T cell epitopes from various viral proteins proven (i) to be frequently and HLA-independently recognized by T cells in COVID-19 convalescents, (ii) to be of pathophysiological relevance for T cell immunity to combat COVID-19, and (iii) to mediate long-term immunity after infection (Nelde et al. Nat Immunol 2021, Bilich et al. Sci Transl Med 2021). CoVac-1 vaccine peptides are adjuvanted with the novel toll-like receptor 1/2 agonist XS15 emulsified in Montanide࣪ ISA51 VG. In a first-in-human clinical trial in healthy adults (NCT04546841), CoVac-1 showed a favorable safety profile and induced profound and long-lasting T cell immunity after single dose administration in 100% of the study subjects, mediated by multifunctional T-helper 1 CD4+ and CD8+ T cells. CoVac-1-induced T cell responses surpassed those after SARS-CoV-2 infection as well as those after vaccination with approved vaccines and were unaffected by current SARS-CoV-2 variants of concern (Heitmann et al. Nature 2021). Here we present the interim safety and immunogenicity results of our Phase I/II trial evaluating CoVac-1 in patients with congenital or acquired B cell deficiency, mainly comprising leukemia and lymphoma patients (NCT04954469). 64% of study subjects had previously been vaccinated with approved vaccines without developing any humoral immune response. Alike in the healthy adults, CoVac-1 showed a good safety and tolerability profile without relevant systemic adverse events. CoVac-1-specific T cell responses could be documented in 93% of study subjects on day 28 after CoVac-1 application, with earliest responses evidenced at day 14 (71%). Vaccine-induced T cell responses were mediated by multifunctional T-helper 1 CD4+ T cells. Of note, CoVac-1 induced T cell responses in this highly immune compromised study population were similar to those occurring in healthy volunteers after natural infection or induced by approved vaccines. These results identify CoVac-1 as promising vaccine candidate for cancer and other immunocompromised patients with immunoglobulin deficiency. Recruitment of the Phase II part of the trial is ongoing with results expected for March 2022. Citation Format: Claudia Tandler, Jonas S. Heitmann, Maddalena Marconato, Yacine Maringer, Monika Denk, Marion Richter, Annika Nelde, Imma Fischer, Markus W. Löffler, Hans-Georg Rammensee, Helmut R. Salih, Juliane S. Walz. Interim safety and immunogenicity results of a phase I trial evaluating the multi-peptide COVID-19 vaccine candidate CoVac-1 for induction of SARS-CoV-2 T cell immunity in cancer patients with disease- or treatment-related immunoglobulin deficiency [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2022; 2022 Apr 8-13. Philadelphia (PA): AACR; Cancer Res 2022;82(12_Suppl):Abstract nr CT258.