CoVac-1, a multipeptide COVID-19 vaccine candidate, elicited immunogenicity in patients with cancer and disease-related or treatment-related immunoglobulin deficiency in a phase I/II trial reported at the American Association for Cancer Research (AACR) Annual Meeting 2022.1 These patients are unable to mount an antibody immune response to existing vaccines that is sufficient for protection against COVID-19, including those with hematologic malignancies, those undergoing transplantation, and elderly individuals. In this study and earlier phase I/II clinical trials, CoVac-1 (a T-cell activator) induced T-cell responses at day 28 after administration in a majority of patients enrolled.2
“The intensity of CoVac-1–induced T-cell responses is exceeding that seen in mRNA-vaccinated immunocompromised individuals and is comparable to that seen in immune-competent COVID-19 convalescents,” stated Claudia Tandler, MSc, a PhD candidate in the Clinical Collaboration Unit of Translational Immunology at the University Hospital Tubingen, Germany, who presented the study at the AACR meeting.
The main goal of developing CoVac-1 was to induce superior T-cell immunity and to protect high-risk populations, such as patients with cancer, from severe COVID-19.— Claudia Tandler, MSc
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Study Background
“To our knowledge, CoVac-1 is currently the only peptide-based COVID-19 vaccine candidate being developed and evaluated for immunocompromised patients,” Ms. Tandler explained. She and her team explored the use of the vaccine to induce a T-cell response against SARS–CoV-2, potentially providing long-term immunity and combating severe COVID-19 infection, even in cases where antibodies are absent.
“T cells are very important in the antiviral immune response, both in the acute setting and for long-term immunity. This is particularly important for patients lacking humoral immunity who are unable to mount a sufficient immune response. This includes patients with lymphoma or leukemia and those with congenital or acquired immune defects, as well as those undergoing transplantation,” she said.
“The main goal of developing CoVac-1 was to induce superior T-cell immunity and to protect high-risk populations, such as patients with cancer, from severe COVID-19,” Ms. Tandler noted.
“The biological principle of this vaccine is based on the fact that T cells are activated upon binding to target [human leukocyte antigen (HLA)] peptides. So, SARS–CoV-2 enters a host cell and is then naturally digested inside the cell,” Ms. Tandler explained. “Small viral fragments are then presented at the cell surface by HLA molecules, where they can be recognized by peptide-specific T cells. The target antigens were identified based on analysis of T-cell responses in a large cohort of COVID-19 convalescents,” she noted.
Six HLA-DR peptides were selected for clinical research. The peptides were derived from different viral components and covered multiple HLA-DR allotypes to offer allotype-independent application. The vaccine includes a novel adjuvant, the Toll-like receptor 1/2 agonist XS15 emulsified in Montanide™ ISA 51 VG. According to Ms. Tandler, these novel adjuvants build a depot at the vaccination site, preventing the peptides from degradation and enabling long-lasting stimulation.
First-in-Human Trial
CoVac-1 is given as a single-dose subcutaneous injection into the skin of the abdomen. The first-in-human clinical trial, previously reported in Nature, enrolled 12 healthy adults aged 18 to 55 in part 1 and 24 healthy adults aged 56 to 80 in part 2.2 As expected, local reactions occurred, but there were no inflammatory systemic adverse events.
Both the safety and efficacy of the vaccine were assessed until day 56. To assess immunogenicity, blood was collected at baseline (day 1) as well as on days 7, 14, 28, and 56, and at months 3 and 6. Peripheral blood mononuclear cells from the blood draws were isolated to test the T-cell responses.
“We observed T-cell responses in 100% of participants at day 28, and follow-up analyses showed that T-cell responses persisted until month 3 in all participants,” she said. “The intensity of the T-cell responses appeared to exceed that of COVID-19 convalescents and COVID-19–vaccinated individuals. Further, responses were not affected by any of the COVID-19 variants of concern, including Omicron.”
Second Clinical Trial
A second combined phase I/II study of CoVac-1 included 54 patients; 50 patients had cancer (including leukemia and lymphoma), and 4 had congenital B-cell deficiency. Precisely 87% of the patients had been previously vaccinated with an approved COVID-19 vaccine, but none developed an antibody response. In part 1, the study assessed the primary endpoint of safety/tolerability in 14 patients. In part 2, which included 40 patients, the primary endpoint was efficacy determined by the induction of SARS–CoV-2–specific T cells.
“We further characterized the T-cell response, and the CoVac-1–induced CD4 T cells displayed 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,” she continued.
The T-cell response observed in the study exceeded that of mRNA-vaccinated patients who were immunocompromised. Moreover, according to Ms. Tandler, the low-level spike-specific T-cell responses that were observed after vaccination with COVID-19 mRNA vaccine could further be boosted and expanded to other viral proteins.
To ascertain whether the T-cell response generated by the peptide vaccine could protect immunocompromised patients, the research team compared the intensity of the CoVac-1–induced T-cell response with that of healthy individuals who were convalescent from COVID-19. The responses were comparable to those in the healthy COVID-19 convalescents.
“Based on these promising results, we are currently preparing a phase III approval trial, because CoVac-1 has the potential to help to protect this highly immunocompromised patient cohort from severe COVID-19,” Ms. Tandler told listeners. She said the investigators hope to expand the patient cohort to include people from other countries.
Expert Point of View
Ana Maria Lopez, MD, MPH
Press conference moderator Ana Maria Lopez, MD, MPH, of Sidney Kimmel Cancer Center–Jefferson Health, said: “We know there are patients who may not be able to mount an immune response to existing vaccines, such as those with hematologic malignancies. Having an option for these groups is critical. This vaccine has the potential to benefit patients with cancer as well as other immunosuppressed populations, such as people with autoimmune disease and elderly people.”
Dr. Lopez added: “This vaccine is a first step. We don’t yet know what happens with [SARS–CoV-2] exposure. The vaccine needs to be tested further, but a peptide vaccine appears to be a novel way to stimulate the immune response,” she said.
DISCLOSURE: Ms. Tandler reported no conflicts of interest. Dr. Lopez has received research funding from Bristol-Myers Squibb.
REFERENCES
1. Tandler C, Heitmann JS, Marconato M, et al: Interim safety and immunogenicity results of a phase I trial evaluating the multipeptide 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. AACR Annual Meeting 2022. Abstract CT258. Presented April 12, 2022.
2. Heitmann SJ, Bilich T, Tandler C, et al: A COVID-19 peptide vaccine for the induction of SARS–CoV-2 T cell immunity. Nature 601:617-622, 2021.
