d See Table 2 . e MLF = mucosal lining fluid , will be collected using a synthetic ab sorpt ive matrix [39] f Participants will complete a questionnaire for solicited systemic and local AEs on a daily basis from each vaccination until 7 days after each vaccination, see Appendi x 1. g SAEs that occur within 7 days of each vaccination will be reported h Newly developed irAEs [38] grade ≥ 3 need to be reported for cohort B and D up to 28 days after the second vaccination and from the third vaccination to 28 days thereafter . Version number: 6.0, 27 December 2021 27 of 49 i AESIs (see Appendix 2) will be reported by the treating physicians up to 18 months after vaccination for cohorts B -D. j The name of the vaccine, batch number and date and time of administration will be recorded. k Participants will complete a questionnaire for diagnosis of SARS -CoV-2 infection, severity and outcome of COVID -19. l Only participants with an inadequate antibody response (≤ 300 BAU/mL) on day 28 after the second vaccination. Table 2: Blood tests Vacc1a Vacc2a Day 28 Vacc2 Day 180 Vacc3ad Day 28 vacc3 Day 330 Day 540 SARS -Cov-2 antibodies x x x x x x x x PBMC isolation for in depth cellular immune response x x x x x x x Routine hematologyb x x x x x x x x Routine chemistryc x x x x x PBMC = peripheral blood mononuclear cells a Blood has to be drawn before vaccination b Hemoglobin , red blood cell count, platelet count, white blood cell count, white blood cell differential c glucose, creatinine, aspartate aminotransferase ( ASAT ), alanine aminotransferase (ALAT ), albumin, lactate dehydrogenase ( LDH), C-reactive protein ( CRP ). d Only participants with an inadequate antibody response (≤ 300BAU/mL) on day 28 after the second vaccination. 8.4 Withdrawal of individual subjects Subjects can leave the study at any time for any reason if they wish to do so without any consequences. The investigator can decide to withdraw a subject from the study for urgent medical reasons. 8.4.1 Specific criteria for withdrawal (if applicable) Not applicable Version number: 6.0, 27 December 2021 28 of 49 8.5 Replacement of individual subjects after withdrawal Not applicable 8.6 Follow -up of subjects withdrawn from treatment Participants who receive at least one dose of the vaccine will be monitored for AEs, SAEs, AESIs and ir AEs according to the protocol (up to day 7 after each vaccination for cohort s A and C and up to day 28 after the last vaccination for cohort s B and D). If the subject does not withdraw consent , also blood samples will be drawn according to the protocol. 8.7 Premature termination of the study Not applicable since vaccination is standard of care. 9. SAFETY REPORTING 9.1 Temporar y halt for reasons of subject safety In accordance to section 10, subsection 4, of the WMO, the sponsor will suspend the study if there is sufficient ground that continua tion of the study will jeopardize subject health or safety. The sponsor will notify the accredited METC wit hout undue delay of a temporary halt including the reason for such an action. The study will be suspended pending a further positive decision by the accredited METC . The investigator will take care that all subjects are kept informed. 9.2 AEs, AESIs and SUSARs 9.2.1 Adverse events (AEs) AEs are defined as any undesirable experience occurring to a subject during the study , whether or not considered related to COVID -19 vaccination . In this study, solicited AEs will be reported by all participants on a daily basis for 7 days after each vaccination. 9.2.2 Serious Adverse events (AEs) A serious adverse event is any untoward medical occurrence or effect that - results in death; Version number: 6.0, 27 December 2021 29 of 49 - is life threatening (at the time of the event); - requires hospitalisation or prolongation of existing inpatients’ hospitalisation; - results in persistent or significant disability or incapacity; - is a congenital anomaly or birth defect; or - any other important medical event that did not result in any of the outcomes listed above due to medical or surgical intervention but could have been based upon appropriate judgement by the investigator . An elective hospital admission will not be considered as a serio us adverse event. The investigator will report all SAEs that occur within 7 days of administration of the vaccine to the PI without undue delay after obtaining knowledge of the events. The coordinating investigator, the PI or delega ted trial personnel will report the SAEs through the web portal ToetsingOnline to the accredited METC that approved the protocol, within 7 days of first knowledge for SAEs that result in death or are life threatening followed by a period of maximum of 8 da ys to complete the initial preliminary report. All other SAEs will be reported within a period of maximum 15 days after the sponsor has first knowledge of the serious adverse events. 9.2.3 Adverse events of special interest (AESIs) Adverse events of special i nterest (AESIs) and serious adverse events (SAEs) frequently occur in patients with cancer who receive systemic therapy as a result of the cancer treatment or the underlying disease. Therefore, AESIs will be collected in this study (see Appendix 2). Treati ng physicians from patients in cohorts B, C and D will report AESIs to the PI. The coordinating investigator, the PI or delegated trial personnel will report the AESIs through the web portal ToetsingOnline to the accredited METC that approved the protocol, within 15 days after first knowledge of the AESIs. Since the vaccine is a registered agent, and the number of controls in this study is very small compared to the registration trials, AESIs from the control group will not meaningfully add to the existing safety data . Therefore, s ubjects in the control group will be asked to report potential side effects of vaccination according to the national guidelines for the general population t o the Dutch pharmacovigilance center Lareb. Version number: 6.0, 27 December 2021 30 of 49 Death of any cause is considered an AESI, because life expectancy of at least 12 months is required for inclusion. We will report deaths and collect information on cause of death. In order to be as complete as possible , informed consent is asked for coupling of data with the Gemeentelijke Basis Administratie (GBA) and Centraal bureaus voor Statistiek (CBS), also from individuals without cancer. However, this is optional and participants who do not consent to coupling o f data with CBS and GBA can participate in the study. 9.2.4 Immun e related adverse events (ir AEs) irAEs are toxicities from immune checkpoint inhibitors and do not include infusion reactions [ 38]. For patients in cohorts B and D treated with immunotherapy , all irAEs [38] that occur between the first vaccination and 28 days after the last vaccination will be collected and graded according to CTCAE v5.0. irAEs of grade ≥3 are required to be reported to the PI immediately (i.e. no more than 24 hours after learning o f the event). The coordinating investigator, the PI or delegated trial personnel will report grade ≥3 irAEs through the web portal ToetsingOnline to the accredited METc that approved the protocol, within 15 days of first knowledge of the irAEs that result in death or are life -threatening. All other irAEs will be reported within a period of maximum 15 days . 9.2.5 Suspected unexpected serious adverse reactions (SUSAR s) Adverse reactions are all untoward and unintended responses to an investigational product related to any dose administered. Unexpected adverse reactions are SUSARs if the following three conditions are met: 1. the event must be serious : - results in death; - is life -threatening (at the time of the event); - requires hospitalization or prolongati on of existing inpatients’ hospitalization ; - results in persistent or significant disability or incapacity; - is a congenital anomaly or birth defect; or - any other important medical event that did not result in any of the outcomes listed above due to me dical or surgical intervention but could have been based upon appropriate judgement by the investigator. 2. there must be a certain degree of probability that the event is a harmful and an undesirable reaction to the medicinal product under investigation, reg ardless of the administered dose; Version number: 6.0, 27 December 2021 31 of 49 3. the adverse reaction must be unexpected, that is to say, the nature and severity of the adverse reaction are not in agreement with the pro duct information as recorded in the Summary of Product Characteristics (SPC). The sponsor will report expedited the following SUSARs through the web portal ToetsingOnline to the METC:  SUSARs that have arisen in the clinical trial that was assessed by the METC;  SUSARs that have arisen in other clinical trial s of the same sponsor and with the same medicinal product, and that could have consequences for the safety of the subjects involved in the clinical trial that was assessed by the METC. The remaining SUSARs are recorded in an overview list (line -listing) tha t will be submitted once every half year to the METC. This line -listing provides an overview of all SUSARs from the vaccine , accompanied by a brief report highlighting the main points of concern. The expedited reporting of SUSARs through the web portal Eudravigilance or ToetsingOnline is sufficient as notification to the competent authority. The expedited reporting will occur not later than 15 days after the sponsor has first knowledge of the adverse reactions. For fatal or life-threatening cases, the ter m will be maximal 7 days for a preliminary report with another 8 days for completion of the report. 9.3 Annual safety report In addition to the expedited reporting of SUSARs, the sponsor will submit, once a year throughout the clinical trial, a safety report to the accredited METC and competent authority . This safety report consists of:  a list of all suspected (unexpected or expected) serious adverse reactions, along wi th an aggregated summary table of all reported serious adverse reactions, ordered by organ system, per study;  a report concerning the safety of the subjects, consisting of a complete safety analysis and an evaluation of the balance between the efficacy and the harmfulness of the medicine under investigation. Version number: 6.0, 27 December 2021 32 of 49 9.4 Follow -up of AEs All solicited AEs, SAEs, AESIs and irAEs will be followed until they have abated, or until a stable situation has been reached. Depending on the event, follow up may require additional tests or medical procedures as indicated, and/or referral to the general physician or a medical specialist.