Research Yana Debie

Abstract

COVID-19, a disease caused by an infection with SARS-CoV-2, has a broad range of clinical presentations varying from asymptomatic to severe bilateral pneumonia and even death. The risk to develop severe COVID-19 as well as the mortality is the highest in the elderly and in people with a pre-existing condition such as cancer. Hence, cancer patients were prioritized for COVID-19 vaccination even though data on the effectiveness and safety was not available as immunocompromised patients, like cancer patients, were excluded from vaccine approval trials. Since the approval of different COVID-19 vaccines, our group as well as many others performed studies to map the immunological responses of cancer patients after vaccination. In general cancer patients have reduced humoral immune responses after COVID-19 vaccination, nevertheless the vaccines are well-tolerated. As COVID-19 is evolving to be an endemic virus, it is important to map all parts of the vaccination-induced immune response. While most studies report IgG levels and neutralizing antibodies when investigating the humoral immunity, IgA antibodies are important for mucosal immunity and eliminate pathogens immediately at the point of entry (e.g. respiratory system). In the context of influenza, IgA serum levels have been correlated with influenza vaccine efficacy and influenza-specific IgA has been shown to be more effective in preventing infections in mice and humans compared with influenza-specific IgG. Therefore the level of IgA in serum may serve as an indicator of host immune response and might possible be a better predictor for protection against respiratory viruses compared to IgG, but studies on IgA production upon COVID-19 vaccination are lacking. Additionally, studies assessing the role of innate immune cells in vaccination-induced immune response are scarce. A recent study provided the first hints towards the predictive capacity of NK cells -innate lymphocytes that are crucial for mediating anti-viral responses- for vaccine-induced immunity in both healthy individuals and immunocompromised patients without cancer. This is in line with other research highlighting the potential of the activity level of NK cells to serve as a biomarker for a functional immune response, but as NK cells are involved in anti-tumor responses and might be affected by anti-neoplastic treatment, it is currently unknown if these findings can be applied in a cancer population. Hence, the aim of the current study is to gain a more in depth understanding of the different aspects of vaccination-induced immunity against SARS-CoV-2 in cancer patients focusing on both IgA levels and NK cells. This will help guiding COVID-19 vaccination strategies for cancer patients during future endemic outbreaks by providing knowledge on the state of the immune system of cancer patients and their response upon vaccination. Furthermore, the obtained insights can be used to improve vaccination strategies for cancer patients for other viruses as well as when novel viral pathogens emerge.

Researcher(s)

• Promoter: Vandamme Timon
• Co-promoter: Van Audenaerde Jonas
• Fellow: Debie Yana

Research team(s)

• Center for Oncological Research (CORE)

Project type(s)

• Research Project

Abstract

COVID-19 is a disease caused by an infectious outbreak of SARS-CoV-2. It was first reported in the City of Wuhan, People's Republic on 31 December 2019. Today, the virus is widely spread throughout the world and declared by the World Health Organisation (WHO) as a pandemic. There are a broad range of clinical presentations of a viral SARS-CoV-2 infection, ranging from asymptomatic, sensation of a mild cold or flu to severe bilateral pneumonia and death. Cancer patients are at high risk to develop serious illness after infection with SARS-CoV-2. Therefore, it is of high importance to protect these patients by following hygiene measurements and social distancing. But, as indicated by the guidelines of the Belgian and European Society for Medical Oncology, it is also important to vaccinate cancer patients. Although, not many studies that investigated the vaccine efficacy of COVID-19 vaccines in cancer patients have been performed. Due to the cancer or the treatment, it could be possible that the efficacy of the vaccines is lower in cancer patients or that they develop more side effects as a result of vaccination. To investigate this, we will monitor the reaction of the immune system of current and ex oncological and haematological patients on the different COVID-19 vaccines (Pfizer, Moderna, AstraZeneca, Janssen Pharmaceutica). The adverse effects as a reaction on vaccination will be investigated in this population as well. Clinical data of the patients will be collected and a blood drawn will be performed at different time points: before vaccination and 4, 6 and 12 months after receiving the first vaccination dose. The blood samples will be used to determine the amount and efficacy of the antibodies against SARS-CoV-2. Patients will also be asked to report side effects after vaccination. This will be done with a questionnaire that will be sent to the patients three days after each vaccination. The primary endpoint of the study is the quantification of different anti SARS-CoV-2 specific IgG antibodies per study cohort at 4 months after the first vaccination. Depending on the availability, antibody titers will be quantified using a MULTIPLEX SARS-CoV-2 Immunoassay, Siemens Healthineers Atellica IM SARS-CoV-2 IgG (sCOVG) assay or an in-house developed anti-RBD ELISA (Sciensano). The secondary endpoints of the study are to investigate the evolution and duration of the immune response after vaccination in the patient cohort using serological assays to analyse anti-RBD IgG titers 12 months after the first vaccination. Another secondary endpoint is to analyse the titers of neutralizing antibodies both 4,6 and 12 months after receiving the first vaccination dose. Furthermore, it is aimed to investigate the efficacy of the immune response in the patient cohort for each different vaccine. This will be assessed by the SARS-CoV-2 infection rate based on information collected through questionnaires on incidence of (PCR-confirmed or chest CT scan confirmed) SARS-CoV-2 infection within a time frame of 12 months after the start of the study. At last, we will investigate the safety of the different COVID-19 vaccines that are commercially available in Belgium. Safety will be reported in terms of incidence and severity of adverse effects (AEs) using a questionnaire which will be sent via REDCap. Patients will be asked to enter their adverse events over a period of 3 days after the vaccination day. If the patient does not have an email address, the questionnaire can be completed on paper. Only patients who had their baseline visit prior to their vaccination will be asked to complete these questionnaires. To end, serious vaccine-related adverse events which lead to hospitalization or further examination will be reported in the eCRF. This research project will provide knowledge on how the immune reaction after vaccination develops in cancer patients and patients with oncological or haematological history.

Researcher(s)

• Promoter: Peeters Marc
• Fellow: Debie Yana

Research team(s)

• Center for Oncological Research (CORE)

Project type(s)

• Research Project