Patients with cancer and immunoglobulin deficiency have compromised immune systems–based response to COVID-19 vaccines. A team of researchers in Germany has developed a multipeptide COVID-19 vaccine that boosts immunity in immunocompromised patients, according to results of a phase 1/2 trial reported at the 2022 American Association for Cancer Research annual meeting.
The CoVac-1 trial showed promising T-cell activity and safety in patients with cancer who have disease- or treatment-related immunoglobulin deficiency. CoVac-1, a T-cell activator vaccine, is the first peptide-based vaccine to be developed to combat COVID-19 infection.
The goal of the study was to induce T-cell response against SARS-CoV-2 to provide long-term immunity and prevent severe COVID-19 infection in high-risk patients. This is especially important for patients lacking humoral/antibody-based response, explained lead investigator Claudia Tandler, PhDc, Clinical Collaboration Unit of Translational Immunology, Tübingen University Hospital, Germany.
“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, SARS-CoV-2 enters a host cell, and the stem naturally digests inside the cell,” she said. “Small viral fragments are then presented at the cell surface by HLA [human leukocyte antigen] molecules, where they can be recognized by peptide-specific T-cells,” she explained.
Six HLA-DR peptides derived from different viral components were used to develop the vaccine. The vaccine includes a toll-like receptor agonist, XS15, emulsified in Montanide ISA51 VG. These novel adjuvants build a depot at the vaccination site, which prevents the peptides from degradation and allows for long-lasting stimulation.
First Phase 1/2 Trial
CoVac-1 is administered as a single-dose subcutaneous infusion into the skin of the abdomen. In part 1 of the first study, 12 healthy participants between the ages of 18 and 55 years were evaluated; part 2 included 24 healthy participants between the ages of 56 and 60 years.
At day 28 of the first study, T-cell responses were observed in 100% of participants, which persisted until month 3 in all participants. The magnitude of the T-cell responses appeared to be superior to that of COVID-19 convalescence and vaccinated individuals. Furthermore, responses were not affected by any of the present COVID-19 variants of concern, including Omicron.
Patients experienced the expected local reaction to the vaccine, but no systemic inflammatory adverse events (AEs) were observed.
Second Phase 1/2 Trial
A second phase 1/2 study included 54 immunocompromised patients; 50 patients had cancer (leukemia or lymphoma) 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.
Part 1 of the second study evaluated safety and tolerability in 14 patients. Part 2 evaluated efficacy in 40 patients as determined by the induction of SARS-CoV-2–specific T-cells.
Similar to the previous phase 1 study, investigators of the phase 1/2 study expected local reactions, but there were no inflammatory systemic AEs. At day 28, T-cell responses were observed in 86% of the patients.
“We further characterized the T-cell response and the induced CD4+T-cells displayed in desired multifunctional phenotype because they were positive for cytokines such as IL [interleukin]-2, TNF [tumor necrosis factor], and interferon gamma. This resembles the phenotype of T-cells after natural infection,” Ms Tandler explained.
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, she noted.
The data do not prove that the new vaccine protects immunocompromised patients against COVID-19, but the investigators compared the intensity of the CoVac-1–induced T-cell response to that of healthy patients who were convalescent from COVID-19 and the intensity of response was comparable in both groups, suggesting that it will work.
The next step will be to evaluate whether the vaccine actually protects immunocompromised patients. “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,” Ms Tandler said.
