Hantavirus disease Infections and Infestations
Conditions
Interventions
The intervention is vaccination with MVA-Hanta. Participants will be enrolled sequentially in three groups to receive escalating doses of the vaccine, to be given in two administrations, 28 days apart
Sponsors
University Hospital Southampton NHS Foundation Trust
Eligibility
Sex/Gender
All
Age
18 Years to 50 Years
Inclusion criteria
Inclusion criteria: 1. Healthy adults aged 18 to 50 years. 2. Able and willing (in the Investigator’s opinion) to comply with all study requirements. 3. Willing to allow the Investigators to discuss the volunteer’s medical history with their General Practitioner (GP). 4. For females only, willingness to practice continuous effective contraception (see below) during the study and (for females only) a negative pregnancy test on the day(s) of screening and vaccination. 5. Agreement to refrain from blood donation during the course of the study. 6. Provide written informed consent. Female volunteers of childbearing potential are required to use an effective form of contraception for the duration of their participation in the study. Acceptable forms of contraception for female volunteers are as follows: 1. Established use of oral, injected or implanted hormonal methods of contraception 2. Placement of an intrauterine device or intrauterine system 3. Total abdominal hysterectomy or surgical sterilisation 4. Barrier methods of contraception (condom or occlusive cap with spermicide) 5. Male sterilisation if the vasectomised partner is the sole partner for the subject 6. True abstinence when this is in line with the preferred and usual lifestyle of the subject For the purpose of this document, a woman is considered of childbearing potential (WOCBP), i.e. fertile, following menarche and menarche and until becoming post-menopausal unless permanently sterile. Permanent sterilisation methods include hysterectomy, bilateral salpingectomy and bilateral oophorectomy. A postmenopausal state is defined as no menses for 12 months without an alternative medical cause.
Exclusion criteria
Exclusion criteria: 1. Participation in another research study involving receipt of an investigational product in the 30 days preceding receipt of MVA-Hanta, or planned use during the study period. 2. Prior receipt of an MVA-based vaccine or mpox vaccine. 3. Receipt of a licenced vaccine, or other investigational vaccine in the 30 days preceding receipt of MVA-Hanta and which is likely to impact on interpretation of the trial data, as assessed by the investigator. 4. Any medical condition that in the judgment of the investigator would make intramuscular (IM) injection unsafe. 5. Administration of immunoglobulins and/or any blood products within the three months preceding the planned administration of the vaccine candidate. 6. Confirmed or under investigation for immunosuppressive or immunodeficient state, including HIV infection; asplenia; recurrent, severe infections and chronic (more than 14 days) immunosuppressant medication during the period starting 6 months prior to the first vaccine dose. For corticosteroids, this will mean prednisone 20 mg/day (for adult subjects), or equivalent. Inhaled and topical steroids are allowed. 7. Administration of long-acting immune-modifying drugs at any time during the study period (e.g. infliximab). 8. History of Hantavirus anti-viral treatment within 60 days prior to vaccination. 9. History of allergic disease or reactions likely to be exacerbated by any component of the vaccine. 10. Any history of anaphylaxis in relation to vaccination. 11. Pregnancy, lactation or willingness/intention to become pregnant during the study. 12. History of cancer (except basal cell carcinoma of the skin and cervical carcinoma in situ). 13. History of serious psychiatric condition likely to affect participation in the study. 14. Any other serious, chronic illness requiring hospital specialist supervision. 15. Suspected or known current alcohol abuse as defined by an alcohol intake of greater than 42 units every week. 16. Suspected or known injecting drug abuse in the 5 years preceding enrolment. 17. Seropositive for hepatitis B surface antigen (HBsAg). 18. Seropositive for hepatitis C virus (antibodies to HCV). 19. Known positive HIV Test 20. History of clinical Hantavirus infection 21. Any clinically significant abnormal finding on screening biochemistry or haematology blood tests or urinalysis. 22. Any other significant disease, disorder or finding which may significantly increase the risk to the volunteer because of participation in the study, affect the ability of the volunteer to participate in the study/comply with study requirements or impair interpretation of the study data. 23. Inability of the study team to contact the volunteer’s GP to confirm medical history and safety to participate
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| The specific endpoints for safety and reactogenicity will actively and passively collect data on adverse events. The following parameters will be assessed: 1. Occurrence of solicited local reactogenicity signs and symptoms for 7 days following each vaccination. 2. Occurrence of solicited systemic reactogenicity signs and symptoms for 7 days following each vaccination. 3. Occurrence of unsolicited adverse events for 28 days following the first vaccination and for subsequent vaccinations from the time of vaccination through the following 28 days. 4. Change from baseline for safety laboratory measures for 28 days following each vaccination. 5. Occurrence of serious adverse events within 28 days (day of vaccination and 27 subsequent days) after each vaccination and over the whole study duration. 6. Solicited and unsolicited AE data will be collected at each clinic visit. It will be collected from diary cards, clinical review, clinical examination (including observations) and laboratory results. This AE data will be tabulated and the frequency, duration and severity of AEs will be compared between groups. 7. Haematological and biochemical laboratory values will be presented according to toxicity grading scales and tabulated by group. 8. SAEs, AEs of special interest and withdrawal due to AE(s)/SAE(s) will be described in detail | — |
Secondary
| Measure | Time frame |
|---|---|
| 1. The cellular immunogenicity of MVA-Hanta will be measured by testing Peripheral Blood Mononuclear Cells (PBMCs) for interferon-gamma responses to Hantavirus nucleoprotein peptides in an Enzyme-Linked ImmunoSpot (ELISpot) assay 2. The humoral immunogenicity of MVA-Hanta will be measured by testing serum for IgG specific to the Hantavirus nucleoprotein in an Enzyme-Linked Immunosorbent Assay (ELISA) 3. The mucosal immunogenicity of MVA-Hanta will be measured by testing saliva samples in a secretory IgA ELISA 4. Functional antibody responses to Hantavirus, e.g., by virus neutralisation, may also be assessed 5. Anti-vector immunity may also be assessed by ELISA Due to the lack of relevant samples prior to this trial, immunogenicity assays will not be fully validated prior to testing. Assays will have documented Standard Operating Procedures and system suitability acceptance criteria. Samples from this trial will be used to develop and qualify immunogenicity assays against Hantavirus. Measured at 28 days after dose two (day 56) | — |
Countries
United Kingdom
Outcome results
None listed