Zika virus Infections and Infestations
Conditions
Interventions
The IMP is a vaccine administered intramuscularly in clinic. Participants will receive two doses of the IMP. The trial will begin with 5 x 10e7 pfu. Following satisfactory safety reporting and Indepe
Sponsors
University of Liverpool
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: Patients eligible for the trial must comply with all of the following at screening. Inclusion criteria as per protocol provided in brackets: 1. A male or female adult between 18 and 59 years of age at consent 4. No planned re-location or foreign travel during the study period 7. If female, negative pregnancy test at the point of screening and dosing 8. If female, prepared to use an efficacious method of contraception during the study from screening and until 28 days after the last vaccine dose for women of childbearing potential
Exclusion criteria
Exclusion criteria: Any patient meeting any of the criteria listed below at baseline will be excluded from study participation. Exclusion criteria as per protocol provided in brackets: 1. Use of any investigational or non-registered drug within 5 half-lives of the drug, or 30 days preceding administration of study vaccine, whichever is longer 3. Receipt of any biologic agents with mechanisms of action that might affect the immune system, at the discretion of the CI and local PI 4. Administration of immunosuppressants or other immune-modifying drugs within a period of six months before vaccination or at any time during the study period; participants who have received these agents may also be excluded at the discretion of the CI and local PI. 5. Any confirmed or suspected immunosuppressive or immunodeficient condition. 6. A family history of congenital or hereditary immunodeficiency. 7. Any antiviral drug therapy within a period of 5 drug half-lives or 30 days before vaccination, whichever is longer, 8. History of significant allergic reactions likely to be exacerbated by any component of the study vaccine, especially allergic disease or reactions to any previous dose of any vaccine. 9. Any history of anaphylaxis 10. Residence of >6 continuous weeks or 3 months in total in any country where Zika or dengue virus infection is plausible or likely. 11. History of proven or strongly suspected flavivirus infection. 12. Acute disease (for example acute infection) at the time of enrolment or vaccination, if symptoms are rated as anything more significant than a mild adverse event. Entry into the study and/or vaccination may be deferred until the illness has resolved for at least one week. 13. Acute or chronic, clinically significant in the opinion of the investigator, disease in any organ system, as determined by history, physical examination or laboratory testing. 14. Presence of any inflammatory condition that might require immunomodulatory therapy. 15. Recent blood donation (inclusion can be delayed under these circumstances; the participant should be enrolled 16 weeks after their last blood donation. Each participant should give no more than 470 ml per 16 weeks, so regular blood donation should be suspended during the study and can re-commence 1 month after the last study sample). 16. Prior receipt of a vaccinia based vaccine at any time 17. Administration of immunoglobulins or other blood products containing immunoglobulin within the three months preceding the planned administration of vaccine 18. Administration of any other vaccine (e.g. COVID vaccine) within 30 days of vaccination with MVAZIKZB. In this event, screening can by carried out, and dosing can be delayed until 30 days have elapsed. 19. Any autoimmune condition except mild dermatological problems including psoriasis, vitiligo, and mild eczema, asthma, hay fever. 20. History of allergic disease or reactions to vaccine or egg allergy. 21. Any history of angioedema 22. History of cancer 23. History of serious psychiatric condition likely to affect participation in the study. 24. Bleeding disorder or prior history of significant bleeding or bruising following intramuscular injection. 25. Extreme body mass index greater than 40KG per metre squared or less than 18 kilogrammes per metre squared 26. Suspected or known current alcohol abuse defined by greater than 42 units per week. 27. Suspected or known injecting drug use
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Occurrence of serious adverse events (SAEs) relating to the IMP recorded using reported adverse events from source data up to Day 56 | — |
Secondary
| Measure | Time frame |
|---|---|
| 1. The safety, tolerability and reactogenicity of MVAZIKB at up to 1 x 10e8 pfu, measured using blood draws at baseline, days 3, 7, 14 and 28 post each dose of vaccine 2. Solicited systemic AEs post-vaccination, recorded using reported adverse events from source data from 0-7 days 3. Unsolicited systemic AEs by vaccine dose, recorded using reported adverse events from source data from 0-56 days 4. Laboratory measures at baseline, days 3, 7, 14 and 28 post each dose of vaccine, including: 4.1. Spot-forming cells per million over the lower level of quantitation in antigen-stimulated versus negative control wells at 2 and 4 weeks post vaccine doses, measured by interferon-gamma ELISpot 4.2. Number and % of participants with interferon-gamma ELISpot responses above the cut off for a positive assay in antigen-stimulated versus negative control wells at 2 and 4 weeks post vaccine doses 4.3. Neutralising antibody titre, expressed as reciprocal titre to neutralise 50% of infectious virus quantified by 50% tissue culture infectious dose 5. Adverse events of special interest (ascending polyneuropathy) recorded using reported adverse events from source data from 0-7 days 6. Immunogenicity of escalating doses (5 x 10e7 to 1 x 10e8 pfu) of MVAZIKAB in healthy 18-49-year-old adults measured using T cell ELISPOT and neutralising antibody to envelope and non-structural proteins by ELISpot assay at baseline, days 1, 7, 14, 28, 56 7. Neutralising capacity of antibody measured using plaque reduction neutralisation assay at baseline, days 28 and 56 8. T cell-directed response to envelope and non-structural proteins measured using ELISpot assay at baseline, days 1, 7, 14, 28, 56 | — |
Countries
England, United Kingdom
Contacts
Public ContactHayley Hardwick
Outcome results
None listed