Promising T-cell responses and safety has been shown with the CoVac-1 vaccine in patients with cancer who have disease- or treatment-related immunoglobulin deficiency.
Promising T-cell responses and safety has been shown with the multi-peptide COVID-19 vaccine, CoVac-1, in patients with cancer who have disease- or treatment-related immunoglobulin deficiency, according to Claudia Tandler who presented phase 1/2 findings during the AACR Annual Meeting 2022.
Investigators explored the use of a peptide-based T-cell activator to induce T-cell response against SAR-CoV-2 to induce long-term immunity and combat COVID-19 even in cases where antibodies are absent. This is imperative, especially for patients lacking humoral/antibody-based response, according to Tandler, a PhD candidate in the Clinical Collaboration Unit of Translational Immunology at the University Hospital Tubingen in Germany. The overarching goal of developing CoVac-1 was to induce superior T-cell immunity and protect high-risk populations, like patients with cancer, from severe COVID-19.
“The biological principle of such a T-cell activator is based on the fact that T cells are activated upon binding to target peptides. So, SAR-CoV-2 enters a host cell and the stem naturally digests inside the cell,” explained Tandler.“Small viral fragments are then presented at the cell surface by HLA molecules, where they can be recognized by peptide specific T cells. By target antigens, which could be used, such as a T cell activator [that] was identified based on analysis of T-cell responses in a large cohort of COVID-19 convalescence.”
Six human leukocyte antigen (HLA)-DR peptides were developed for clinical research. The peptides were derived from different viral components and covered multiple HLA-DR allotypes to offer allotype-dependent application. The vaccine includes another toll-like receptor agonist, XS15 emulsified in Montanide ISA 51 VG. According to Tandler, these novel adjuvants build a depot at the vaccination site, which prevent the peptides from degradation and allow for long-lasting stimulation.
In clinical trials, CoVac-1 is administered as a single-dose subcutaneous infusion into the skin of the abdomen. Both the safety and efficacy of the vaccine is assessed until day 56. To assess immunogenicity, blood is collected at baseline (day 1) as well as on days 7, 14, 28, 56, and at months 3 and 6. Peripheral blood mononuclear cells from the blood draws are isolated to test the T-cell responses.
In the first study phase 1 of CoVac-1 (NCT04954469), 12 healthy subjects between the ages of 18 and 55 years old were evaluated in part 1, and 24 healthy participants between the ages of 56 and 60 years were evaluated in part 2.
At day 28 of the study, T-cell responses were observed in 100% of participants, which persisted until month 3 in all participants. The intensity of the T-cell responses appeared to exceed that of COVID-19 convalescence and vaccinated individuals. Further, responses were not impacted by any of the present COVID-19 variants of concern, including Omicron, explained Tandler.
In terms of safety/tolerability, investigators saw the expected local reaction to the vaccine, like granuloma, and no systemic inflammatory adverse events (AEs) occurred.
In another phase 1/2 study of 54 patients, 50 patients had cancer and 4 had congenital B-cell deficiency. Eighty-seven percent of the patients had been previously vaccinated with an approved vaccine, but none developed an antibody response. The study assessed the primary end point of safety/tolerability in part 1 with 14 patients included. In part 2, the primary end point was efficacy determined by the induction of SAR-CoV-2 specific T cells.
Similar to the prior phase 1 study, investigators of the phase 1/2 study saw granuloma, which was an expected local reaction. There were no inflammatory systemic AEs. The most common local reactions were erythema, induration granuloma, and itching.
At day 28, T cell responses occurred in 86% of the patients. Tandler stated, “We further characterize the T-cell response and the induced CD4T cells displayed in desired multifunctional phenotype because they were positive for cytokines such as IL-2, TNF, and interferon gamma. This resembles the phenotype of T cells after natural infection.”
The T-cell response observed in the study exceeded that of mRNA vaccinated patients who were immunocompromised. Moreover, the low-level spike-specific T-cell responses that were observed after vaccination with mRNA vaccine could be boosted and expanded to other viral proteins, according to Tandler.
The data collectively raise the question of how the T-cell response can protect patients who are immunocompromised. To answer the question, Tandler et al compared the intensity of the CoVac-1-induced T-cell response to that of healthy patients who were convalescent from COVID-19.
“We observed that the intensity of the CoVac-1-induced T-cell responses is comparable with those in the healthy cohort. Based on these promising results, we are currently preparing a phase 3 approval trial because CoVac-1 has the potential to help to protect this highly immunocompromised patient cohort from severe COVID-19.”
Tandler C, Heitmann JS, Marconato M, et al. 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. Presented at: 2022 AACR Annual Meeting; April 8-13, 2022; New Orleans, LA. Abstract CT258.