CoVac-1 has promising results in patients with cancer-related immunoglobulin deficiency

CoVac-1, a multipeptide COVID-19 vaccine, American Association for Cancer Research (AACR) 2022 Annual Meeting..

Researchers have considered using peptide-based T cell activators to induce a T cell response to SAR-CoV-2, induce long-term immunity in the absence of antibodies, and fight COVID-19. bottom. This is especially essential for patients without humoral / antibody-based responses, according to Tandler, a PhD candidate for the Clinical Collaborative Research Unit in Translation Immunology at the University of Tubingen Hospital in Germany. The comprehensive goal of developing CoVac-1 was to induce superior T cell immunity and protect high-risk populations such as cancer patients from severe COVID-19.

“The biological principle of such T cell activators is based on the fact that binding to a target peptide activates T cells, so SAR-CoV-2 enters the host cell and the stem It is naturally digested in the cell, “explains Claudia Tandler. “Then, small viral fragments are presented on the cell surface by HLA molecules and recognized by peptide-specific T cells, depending on available target antigens such as T cell activators. [that] It was identified based on an analysis of T cell responses in a large cohort of COVID-19 convalescents. “

Six human leukocyte antigen (HLA) -DR peptides have been developed for clinical research. Peptides are derived from a variety of viral components and have covered multiple HLA-DR allotypes to provide allotype-dependent applications. The vaccine contains another Toll-like receptor agonist, XS15, emulsified in Montanede ISA51VG. According to Tandler, these new adjuvants build a depot at the vaccination site, prevent peptide degradation and allow long-term irritation.

In clinical trials, CoVac-1 is given as a single subcutaneous injection into the skin of the abdomen. Both the safety and efficacy of the vaccine will be assessed up to day 56. To assess immunogenicity, blood is collected at baseline (Day 1) and at Days 7, 14, 28, 56, and 3 and 6 months. Peripheral blood mononuclear cells Cells from blood draws are isolated to test T cell responses.

In Phase 1 of the first study of CoVac-1 (NCT04954469), 12 healthy subjects aged 18-55 years were evaluated in Part 1 and 24 healthy participants aged 56-60 years were evaluated in Part 2. I did.

On day 28 of the study, a T cell response was observed in 100% of participants and persisted until 3 months in all participants. The intensity of the T cell response appeared to exceed that of COVID-19 convalescent and vaccinated individuals. In addition, the response was unaffected by any of the current COVID-19 variants, including Omicron, Tandler explained.

From a safety / tolerability perspective, the researchers confirmed the expected local response to vaccines such as granulomas, with no systemic inflammatory adverse events (AEs).

In another phase 1/2 study of 54 patients, 50 patients had cancer and 4 had congenital B cell deficiency. Eighty-seven percent of patients were vaccinated with a previously approved vaccine, but none showed an antibody response. This study evaluated the primary safety / tolerability endpoints of Part 1 in 14 patients. In Part 2, the primary endpoint was efficacy determined by induction of SAR-CoV-2 specific T cells.

As in previous Phase 1 trials, researchers in Phase 1/2 trials saw a possible local reaction, granulomas. There was no inflammatory systemic AE. The most common local reactions were erythema, indurated granulomas, and itching.

On day 28, a T cell response occurred in 86% of patients. Tandler said: “The T cell response and induced CD4 T cells are positive for cytokines such as IL-2, TNF, and interferon gamma, so they appear in the desired multifunctional phenotype. This is the representation of T cells after spontaneous infection. Similar to a mold. “

The T cell response observed in this study exceeded that of immunocompromised mRNA vaccinated patients. In addition, according to Tandler, the low levels of spike-specific T cell responses observed after vaccination with the mRNA vaccine can be boosted and spread to other viral proteins.

Collectively, the data raise the question of how T cell responses can protect immunocompromised patients. To answer the question, Tandler et al. Compared the intensity of the CoVac-1 evoked T cell response with the intensity of healthy patients in convalescence from COVID-19.

“It was observed that the intensity of the T cell response induced by CoVac-1 was comparable to that of a healthy cohort. Based on these promising results, CoVac-1 is this highly immunodeficient. We are currently preparing a Phase 3 approval trial as it may help protect the patient cohort from severe COVID-19. “

reference:

Tandler C, Heitmann JS, Marconato M, et al. CT258-Evaluating the multipeptide COVID-19 vaccine candidate CoVac-1 for the induction of SARS-CoV-2 T cell-mediated immunity in patients with disease or treatment-related immunoglobulin deficiency cancer. Intermediate safety and immunogenicity results of Phase I trials. Announcement location: 2022 AACR Annual Meeting. April 8-13, 2022. New Orleans, Louisiana. Abstract CT258.