New COVID-19 Vaccine Focused on T-Cell Response Shows Promise in Patients with Cancer

Although vaccination provides a broad immune response against the SARS-CoV-2 virus in most recipients, approved vaccines have shown decreased efficacy in several immunocompromised populations, including patients undergoing treatment for hematologic malignancies.

At the American Association for Cancer Research 2022 Annual Meeting, researchers presented results from a phase 1/2 clinical trial that showed promising results with CoVac-1, the first peptide-based vaccine, in patients with B-cell deficiencies, including many individuals with leukemia and lymphoma.

The goal of the study was to induce T-cell response against the SARS-CoV-2 virus 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 trial investigator Claudia Tandler, PhDc, Clinical Collaboration Unit of Translational Immunology, Tübingen University Hospital, Germany, who presented the findings at the meeting.

“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 said.

To develop CoVac-1, the researchers chose 6 specific antigens from different viral components. The vaccine includes a toll-like receptor agonist, XS15, emulsified in ISA51 VG. These novel adjuvants build a depot at the vaccination site, which prevents the peptides from degradation and allows for long-lasting stimulation.

Study Details

The researchers had previously tested the safety and preliminary efficacy of CoVac-1 in individuals without immune deficiency and found that all those who received the vaccine maintained strong T-cell responses 3 months after vaccination, including responses against Omicron and other SARS-CoV-2 variants of concern. Patients experienced the expected local reaction to the vaccine, but no systemic inflammatory adverse events were observed. Based on these encouraging results, the researchers decided to evaluate the vaccine’s efficacy in immunocompromised patients by carrying out a phase 1/2 study.

Part 1 of the current phase 1/2 trial included 14 patients with a B-cell deficiency (median age, 65 years; N = 12 with leukemia or lymphoma), including 9 patients who previously received a vaccine that failed to elicit a humoral immune response. Part 2 included an additional 40 patients (median age, 61 years; N = 38 with leukemia, lymphoma, or other cancers), 32 of whom had received an approved vaccine but did not develop an antibody response.

Patients enrolled in the trial were administered a single dose of the CoVac-1 vaccine and were monitored for up to 6 months for safety and immunogenicity.

Findings from the safety analysis showed expected local adverse events (eg, erythema, induration granuloma, itching) but no inflammatory systemic adverse events.

Results of the immunogenicity analysis showed T-cell immune responses in 62% of patients 14 days after vaccination and 86% of patients after 28 days.

“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-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 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.

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