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.

FusionVAC22_01: a phase I clinical trial evaluating a DNAJB1-PRKACA fusion transcript-based peptide vaccine combined with immune checkpoint inhibition for fibrolamellar hepatocellular carcinoma and other tumor entities carrying the oncogenic driver fusion

“…XS15-adjuvanted vaccines were evaluated in several trials in healthy individuals (NCT04546841), cancer patients with B cell/antibody deficiency (NCT04954469), glioblastoma patients (NCT04842513) and patients with chronic lymphocytic leukemia (NCT02802943). Here, peptide vaccines adjuvanted with the TLR1/2 ligand XS15 (50µg) emulsified 1:1 in Montanide ISA 51 VG were proven to be safe and effective to induce profound and long lasting CD4 + and CD8 + T cell responses that by far exceeded those induced by previous peptide vaccines as well as by mRNA-based vaccines ( 45 , 46 , 75 , 76 ). In line with that, application of a DNAJB1-PRKACA fusion transcript-based peptide-vaccine adjuvanted with the TLR1/2 agonist XS15 emulsified in Montanide ISA 51 VG in one FL-HCC patient was well tolerated and showed the induction of profound and long-lasting T-cell responses accompanied by long-term disease-free survival ( 36 ).…”

A Synthetic SARS-CoV-2-Derived T-Cell and B-Cell Peptide Cocktail Elicits Full Protection against Lethal Omicron BA.1 Infection in H11-K18-hACE2 Mice

“…Furthermore, conserved proteins can be used to select effective T-cell epitopes for a universal and antimutation vaccine strategy. The published data of CoVac-1 from phase I trial indicated that the CoVac-1 vaccine candidate has a favorable safety profile and induces potent T-cell responses after a single subcutaneous vaccination ( 18 ), and a phase I/II trial reported promising T-cell responses and safety in patients with cancer or immunoglobulin deficiency ( 32 ). CoVepiT and Pep-GNP-SARS-CoV-2 are both HLA-I T-cell multiepitopic peptide vaccines in phase I clinical trials ( 53 ).…”

“…The importance of SARS-CoV-2 T-cell immunity is increasingly recognized, and the induction of T-cell immunity is a central goal for COVID-19 vaccine development. Eliciting T-cell responses with peptide vaccination is more straightforward, since T lymphocytes usually recognize small linear epitope regions of 8 to 15 amino acids of these antigens presented by antigen-presenting cells (APCs) with the major histocompatibility complex (MHC) molecules, which can be mimicked by peptides ( 31 , 32 ). CoVac-1, a T-cell epitopic peptide-based vaccine candidate developed by University Hospital Tübingen, which consists of SARS-CoV-2 human leukocyte antigen DR (HLA-DR) T-cell epitopes from different viral proteins, is currently undergoing phase II clinical trials and considered the most promising COVID-19 T cell vaccine ( 18 ).…”

Forensic and Pharmaceutical Risks in the Organization of Pharmacotherapy of Covid, Post-Covid and Long-Covid Disorders. COVID-19 and Vaccination Practice Standards.

“…The participation of cytokines produced by Th2 cells is associated with viral persistence and chronicity of the process, while the participation of cytokines produced by Th1 cells is associated with the recovery and elimination of the pathogen [93].…”