CHEKOV: CHEcKpoint Inhibitor effects On SARS-CoV-2 Vaccination
Lead Research Organisation:
University of Birmingham
Department Name: Institute of Immunology & Immunotherapy
Abstract
The immune system of cancer patients is affected by their disease but also from side effects of their treatment. A new class of anti-cancer drugs, immune checkpoint inhibitors (ICIs), are very different to all other treatments because they work by directly altering the immune system to target the cancer. These drugs are now used routinely to treat patients with various cancers. They can also cause side effects that could be enhanced by SARS-CoV2 infection or vaccination. There is very little known about how ICIs impact vaccination against SARS-CoV-2. Given that COVID-19 is likely to circulate for the foreseeable future, it is important to know if current COVID-19 vaccines are effective in patients receiving ICIs.
To address this question, we have been collecting blood samples from melanoma patients being treated with ICIs that were infected during the pandemic. More recently we collected samples from ICI-treated melanoma patients and healthy individuals during the COVID-19 vaccination campaign. We now wish to test these samples to see if vaccination of ICI-treated patients illicits the same magnitude and quality of immune response as observed in healthy individuals, or if different vaccines and/or different vaccine scheduling may be required to protect these patients. We will also examine if vaccination or infection of patients receiving ICIs could increase the risk of developing the immune-driven side effects that can be caused by these drugs.
To address this question, we have been collecting blood samples from melanoma patients being treated with ICIs that were infected during the pandemic. More recently we collected samples from ICI-treated melanoma patients and healthy individuals during the COVID-19 vaccination campaign. We now wish to test these samples to see if vaccination of ICI-treated patients illicits the same magnitude and quality of immune response as observed in healthy individuals, or if different vaccines and/or different vaccine scheduling may be required to protect these patients. We will also examine if vaccination or infection of patients receiving ICIs could increase the risk of developing the immune-driven side effects that can be caused by these drugs.
Technical Summary
Data on the effectiveness of prophylactic vaccination in cancer patients is limited. Patients receiving Immune Checkpoint Inhibitors (ICIs) are likely to differ from other groups due to the unique mode of action of these agents: blocking homeostatic controls that normally limit T-cell response generation and effector functions, which include direct cytotoxicity but also providing B-cell help essential for establishing effective antibody responses. It is unknown whether ICI-exposure affects the size and quality of the T-cell/antibody response to SARS-CoV-2 infection and vaccination, possibly skewing them away from virus control to enhance immune pathology, and, conversely, whether virus infection alters ICI-induced immunity including patterns associated with auto-immunity.
We will describe the immune interactions between ICI treatment and immunity to SARS-CoV-2 infection and vaccination using an already established blood sample collection from well-defined cohorts including: i) healthy donors pre- and post-vaccine, ii) serial samples from people with melanoma (with linked clinical data) receiving ICIs pre- and post-vaccine, and iii) melanoma patients infected with SARS-CoV-2 while treated with ICIs. We will first measure IgG, IgA and neutralising antibody responses to spike and nucleocapsid antigens using MesoScale assays. This will provide a rapid initial assessment of vaccine efficacy in patients. We will then characterise T-cell responses to overlapping peptide pools spanning the open reading frames of the main virally encoded T-cell antigens (spike, nucleocapsid and matrix proteins) using an established intracellular cytokine assay capable of measuring six effector functions (IFN-g, TNF-a, IL-4, IL-10, IL-17, and cytotoxic degranulation by surface exposure of CD107a) on CD8+ and CD4+ T-cells.
We will describe the immune interactions between ICI treatment and immunity to SARS-CoV-2 infection and vaccination using an already established blood sample collection from well-defined cohorts including: i) healthy donors pre- and post-vaccine, ii) serial samples from people with melanoma (with linked clinical data) receiving ICIs pre- and post-vaccine, and iii) melanoma patients infected with SARS-CoV-2 while treated with ICIs. We will first measure IgG, IgA and neutralising antibody responses to spike and nucleocapsid antigens using MesoScale assays. This will provide a rapid initial assessment of vaccine efficacy in patients. We will then characterise T-cell responses to overlapping peptide pools spanning the open reading frames of the main virally encoded T-cell antigens (spike, nucleocapsid and matrix proteins) using an established intracellular cytokine assay capable of measuring six effector functions (IFN-g, TNF-a, IL-4, IL-10, IL-17, and cytotoxic degranulation by surface exposure of CD107a) on CD8+ and CD4+ T-cells.
