Yellow fever virus strain 17D-204 (live, attenuated) for Yellow fever

Inclusion criteria

• {"criterion_text":"- >/=18 to ≤50 years of age\n- BMI >/=18,5 kg/m2 and ≤35 kg/m2\n- Agreement to refrain from blood donation and other vaccinations 30 days following vaccination\n- Agreement to share and discuss participant’s medical history and medical records when relevant\n- Able and willing to provide written informed consent\n- Willing to use a highly effective method of contraception up to 30 days after study vaccination (in case of women with childbearing potential)."}

Exclusion criteria

• {"criterion_text":"- Participant has a clinically significant acute illness (this does not include minor illnesses such as diarrhea or mild upper respiratory tract infection) or temperature ≥38.0ºC within 24 hours prior to the planned dose of study vaccine; randomization at a later date is permitted at the discretion of the investigator\n- Receipt of any vaccine (licensed or experimental) within 30 days prior to enrolment\n- Any confirmed or suspected immunosuppressive or immunodeficient state (incl. cancer and HIV/HBV infection); asplenia; recurrent severe infections and use of immunosuppressant medication (including antineoplastic and immunomodulating agents or radiotherapy) within the last 6 months prior to enrolment, except topical or short-term oral steroids (<2 weeks of daily receipt of 20 mg of prednisone or equivalent). Refer to annex 1 for a list of immunosuppressive medication\n- Severe and/or uncontrolled cardiovascular disease, respiratory disease, gastrointestinal disease, liver disease, renal disease, endocrine disorder, psychiatric and neurological illness (mild/moderate well controlled comorbidities are allowed)\n- History of anaphylaxis, allergic disease or reactions to any component of the study vaccine, including eggs or chicken proteins\n- History of acute polyneuropathy (eg, Guillain-Barré syndrome)\n- History of bleeding disorder (e.g. factor deficiency, coagulopathy or platelet disorder), or prior history of significant bleeding or bruising following IM injections, SC injections or venipuncture\n- History of thymus dysfunction (including myasthenia gravis, thymoma) or thymectomy\n- Any other significant disease, disorder, planned surgery, or finding which may significantly affect the ability of the volunteer to participate in the study or impair interpretation of the study data\n- Suspected or known alcohol or drug dependency\n- Participants who are currently on anticoagulant therapy\n- Participants who are continuously using systemic antivirals\n- Subjects with a confirmed flavivirus infection in the past\n- Subjects who already received a flavivirus vaccination prior to enrolment or are planning a flavivirus vaccination during the course of the trial other than the study vaccination.\n- Subjects who received immunoglobulins and/or any blood or blood derived products within 3 months preceding study vaccination (or planned administration during the study)\n- Active participation in another interventional clinical study with active substance intake or large medical procedures affecting the study procedures during the trial or 1 month prior to enrolment\n- Individuals who are working at the investigational site or within the research team of this study and their close relatives\n- Tendency to keloid (scar) formation in response to skin damage\n- Skin diseases or tattoo at the biopsy or vaccination site\n- In the opinion of the investigator, unlikely compliance to the requirements of the study"}

Primary endpoints

• {"endpoint_text":"- The percentage of YFV-specific T cells within the skin-resident lymphocyte parent population at D28, measured by flow cytometry.","definition_or_measurement_approach":"Measured by flow cytometry; outcome assessed at Day 28 within the skin-resident lymphocyte population to determine percentage of YFV-specific T cells."}
• {"endpoint_text":"- The absolute number of YFV-specific T cells within the skin-resident lymphocyte parent population at D28, measured by flow cytometry.","definition_or_measurement_approach":"Measured by flow cytometry; outcome assessed at Day 28 to determine absolute number of YFV-specific T cells in the skin-resident lymphocyte population."}

Secondary endpoints

• {"endpoint_text":"- Percentage and absolute number of circulating and YFV-specific TCM and TEM cells within the CD3+ lymphocyte parent population at D28, and increase in their percentage and absolute number from D0 to D28.","definition_or_measurement_approach":"Flow cytometry evaluation of circulating YFV-specific central-memory (TCM) and effector-memory (TEM) T cells in CD3+ population at D0 and D28; comparison of percentage and absolute number change."}
• {"endpoint_text":"- Percentage and absolute number of YFV-specific TRM, TCM and TEM CD4+ and CD8+ T cells within the skin-resident or CD3+ lymphocyte parent population at D28.","definition_or_measurement_approach":"Flow cytometry to quantify YFV-specific tissue-resident memory (TRM), central-memory (TCM) and effector-memory (TEM) CD4+ and CD8+ T cells in skin-resident or CD3+ populations at Day 28."}
• {"endpoint_text":"- The serum dilutions at which 50% viral neutralization occurs (NT50) as measured by the certified VNT (virus neutralization test) assays at D28, and the increase in their percentage and absolute number from D0 to D28.","definition_or_measurement_approach":"Virus neutralization test (VNT) to determine NT50 titres at D0 and D28 and assess increase to D28."}
• {"endpoint_text":"- The nAbs NT50 titres, IFNy+ spot forming units (SFU) and IFNy/TNF-a/IL-2+ SFU at D0, D14, D28 and D120 measured by VNT and ELISpot/fluorospot respectively.","definition_or_measurement_approach":"VNT for neutralizing antibody NT50 titres; ELISpot/fluorospot for IFN-γ+ SFU and polyfunctional (IFN-γ/TNF-α/IL-2)+ SFU at specified timepoints D0, D14, D28, D120."}
• {"endpoint_text":"- At all timepoints, the NT50 of VNT testing and IFNy+ spot forming units (SFU) and IFNy/TNF-a/IL-2+ SFU. In addition at D0 and D28 , the percentage and absolute number of YFV-specific TRM, TCM and TEM cells within the CD3+ lymphocyte parent population.","definition_or_measurement_approach":"Combined VNT and ELISpot/fluorospot assessments across timepoints; flow cytometry at D0 and D28 for cellular subsets in CD3+ population."}
• {"endpoint_text":"- The occurrence of solicited and unsolicited local Adverse Events (AEs) [Up to Day 28 after vaccination]","definition_or_measurement_approach":"Collection and recording of solicited and unsolicited local AEs up to Day 28 post-vaccination."}
• {"endpoint_text":"- The occurrence of solicited and unsolicited systemic AEs [Up to Day 28 after vaccination]","definition_or_measurement_approach":"Collection and recording of solicited and unsolicited systemic AEs up to Day 28 post-vaccination."}
• {"endpoint_text":"- The occurrence of Serious Adverse Events (SAE’s) [Up to D120]","definition_or_measurement_approach":"Monitoring and recording of SAEs up to Day 120 post-vaccination."}
• {"endpoint_text":"- The occurrence of solicited and unsolicited local Adverse Events (AEs) [Up to Day 28 after vaccination]","definition_or_measurement_approach":"Duplicate listing: collection/recording of solicited and unsolicited local AEs up to Day 28."}
• {"endpoint_text":"- The occurrence of solicited and unsolicited systemic AEs [Up to Day 28 after vaccination]","definition_or_measurement_approach":"Duplicate listing: collection/recording of solicited and unsolicited systemic AEs up to Day 28."}
• {"endpoint_text":"- The absolute number of YFV-specific TRM, TCM and TEM cells at D28","definition_or_measurement_approach":"Flow cytometry quantification of absolute numbers of YFV-specific TRM, TCM and TEM cells at Day 28."}

Methods

• Poster, TV screens and social media (documents: Poster_TV screens and social media) targeting healthy volunteers in Belgium.
• E-mail contact to existing database (documents: E-mail to database_En, E-mail to database_Du) targeting potential participants/volunteers.
• Information on sponsor/clinic website (documents: Info_website_Eng, Info_website_Du) providing trial details and contact information.
• On-site information materials (Info TV screens) at the investigational site.

Belgium

Earliest CTIS Part Ii Submission Date

30-08-2024

Latest Decision Or Authorization Date

24-07-2025

Processing Time Days

328

Number Of Sites

1

Number Of Participants

222

Primary sponsor

Full Name

Institute Of Tropical Medicine

Organisation Type

Hospital/Clinic/Other health care facility

Country Of Registered Address

Belgium