Patients with cancer and immunoglobulin deficiency have compromised response to the available COVID-19 vaccines. A team of researchers in Germany has developed a multipeptide COVID-19 vaccine that boosts immunity in immunocompromised patients, according to the results of a phase 1/2 clinical trial reported at the 2022 American Association for Cancer Research 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 for COVID-19 infection.
The goal of the study was to induce T-cell response against SARS-CoV-2 to provide long-term immunity and to prevent severe disease in high-risk patients. This is especially important for patients lacking humoral or antibody-based response, explained lead investigator Claudia Tandler, MSc, PhD student, Department of Immunology, University of Tübingen, 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,” Ms Tandler said.
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 ISA 51 VG. These novel adjuvants build a depot at the vaccination site, which prevent the peptides from degradation and allow for long-lasting stimulation.
First Phase 1/2 Clinical 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 subjects aged 18 to 55 years were evaluated; part 2 included 24 healthy participants aged 56 to 60 years.
At day 28 of the first study, T-cell responses were observed in 100% of the participants, which persisted until month 3. The magnitude of the T-cell responses was superior to that of patients who had recovered from COVID-19 and COVID-19–vaccinated individuals. Furthermore, the responses were not influenced by any of the present COVID-19 variants of concern, including the Omicron variant.
The patients had the expected local reaction to the vaccine, but no systemic inflammatory adverse events were observed.
Second Phase 1/2 Clinical 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. In all, 87% of the patients had previously received an approved COVID-19 vaccine, but none had an antibody response.
Part 1 of the second study evaluated safety and tolerability in 14 patients. Part 2 of the study 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 adverse reactions, but no inflammatory systemic adverse events were observed. 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 the desired multifunctional phenotype, because they were positive for cytokines such as interleukin-2, 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 the response to the mRNA vaccines in immunocompromised patients. Moreover, the low-level spike-specific T-cell responses observed after vaccination with an 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 had recovered from COVID-19 and the intensity of response was comparable in both groups, suggesting that it will likely be effective.
The next step will be to evaluate whether the vaccine protects immunocompromised patients from getting severe COVID-19.
“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 concluded.