Japanese EncephalitisFlaviPrimeNCT03920111
Flavivirus Cross-priming Potential of IMOJEV
A study testing IMOJEV in people with Japanese Encephalitis, run by University of Liverpool at 1 site in United Kingdom.
Trial summary
There is a pressing need for a better experimental system to understand flavivirus antibody responses, beyond dengue, to make sure the investigators are using current vaccines to greatest effect and to inform the development of next-generation vaccines. Read more about this study
- Who is it for?
- Ages 18 to 70 yearsHealthy volunteers can take part
- Conditions the study is for
- Japanese Encephalitis
- What is being tested?
- IMOJEV
- Type of treatment
- Vaccines
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 19 participants
- Where
- 1 siteUnited Kingdom
- Study dates
- 16 Apr 2021to 11 May 2022
- Phase
- Interventional
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 to 70 years
- All sexes
- Healthy volunteers accepted
- Adult, Older adult
Who may be able to join
- A male or female adult between 18 and 70 years of age at consent.
- Written and informed consent obtained from participant and agreement of participant to comply with the requirements of the study
- Able to attend regularly to donate study blood samples for the duration of the study (8 weeks), no planned re-location or travel to a flavivirus endemic area during the study period.
- Satisfactory medical screen, as demonstrated by study screening document normal physical examination and normal screening blood tests
- Group 1: Any flavivirus exposure status; Group 2: No previous flavivirus vaccination (JE, tick borne encephalitis or yellow fever (YF)), no residence in a flavivirus endemic area nor planned travel to a flavivirus endemic area during the period of the study; Group 3: JE vaccine and/or yellow fever vaccine or other proven flavivirus infection within the last 10 years or other proven flavivirus infection (lifetime).
- An efficacious method of contraception must be used during the study for women of childbearing potential.
Who cannot join
- Use of any investigational or non-registered drug within 5 half-lives of the drug, or 30 days preceding administration of study JE vaccine, whichever is longer; or planned use during the study period.
- Receipt of any investigational biologic agents with mechanisms of action that might affect the immune system, at the discretion of the CI and local PI.
- 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.
- Any confirmed or suspected immunosuppressive or immunodeficient condition.
- A family history of congenital or hereditary immunodeficiency.
- Any antiviral drug therapy within a period of 5 drug half-lives or 30 days before vaccination, whichever is longer, or at any time during the study period.
Show all 19Show fewer
- 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.
- History of having received JE vaccine, yellow fever vaccine, tick-borne encephalitis vaccine or experimental flavivirus vaccine (group 2 only).
- Detectable anti Flavivirus neutralizing antibodies in screening tests (group 2 only).
- 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.
- 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.
- Presence of any inflammatory condition that might require immunomodulatory therapy.
- 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).
- Current or previous abattoir worker or sheep farmer in Scotland (risk of Louping ill virus exposure; group 2 only).
- Administration of immunoglobulins and/or any blood products within the three months preceding administration of vaccine, or planned administration during the study period.
- Seropositive for HIV.
- Pregnancy or Lactation.
- History of excessive alcohol consumption (>28 units per week), drug abuse or significant psychiatric illness.
- Any other condition or consideration that, in the opinion of the Investigator, would pose a health risk to the participant if they were enrolled in the study, or would otherwise interfere with the evaluation of the study aims (e.g. difficult venesection).
Trial locations and contacts
1 site in 1 country.
United Kingdom1 site
Liverpool University Hospitals NHS Foundation Trust
Liverpool, L7 8XP
About this study
Official title: Flavivirus Cross-priming Potential of Live Attenuated Japanese Encephalitis (JE) Vaccine IMOJEV in Flavivirus naïve and Flavivirus Experienced Participants
There is a pressing need for a better experimental system to understand flavivirus antibody responses, beyond dengue, to make sure the investigators are using current vaccines to greatest effect and to inform the development of next-generation vaccines. This study will use live chimeric JE vaccine IMOJEV® as a tool for flavivirus epitope discovery. This will allow experimental JEV infection using replication competent, live, attenuated virus as a model, in a setting where the flavivirus infection history of humans can be tightly controlled.
Read the detailed description
This study will test the hypothesis that in previously flavivirus-exposed individuals, the antibody response is more broadly cross neutralising, and that this will lead to the identification of conserved virion surface epitopes that could be the target of second generation vaccines.
Exploratory Primary Objectives/Specific aims:
- To establish a human model system of JEV infection in healthy adult volunteers using live attenuated JE vaccine IMOJEV®.
- To sort and sequence individual responding B cells (plasmablasts) after vaccination with IMOJEV®, and to generate human monoclonal antibodies to JEV.
- To generate JEV specific human monoclonal antibodies from the sequences derived in (2).
- To describe the development, specificity, cross-reactivity and function of the T cell response to IMOJEV®.
- To establish a sample bank for future work on cross-reactive and other responses to flaviviruses, flavivirus vaccines and other emergent viruses.
Exploratory Secondary Objectives:
- To examine the specificity and cross-reactivity of the antibody response after JE vaccination, using serum and human monoclonal antibodies.
- To determine whether there are epitopes which can serve as the target of broadly cross-neutralising antibody responses.
Experimentally the fine specificity and cross-reactivity of the antibody response will be studied by cloning antibodies from plasmablasts (B cells responding to the vaccine) that have been single cell sorted by flow cytometry then sequenced at one week post vaccine. These human monoclonal antibodies will then be mapped on to the surface of the virus particle using established approaches, and tested to look for cross-reactive antibodies. T cell responses to the vaccine will be studied using custom pools of synthetic peptides by ELISpot and flow cytometry.
- Conditions
- Japanese Encephalitis
- Being tested
- IMOJEV
- Medical subject headings
- Encephalitis, Japanese
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
IMOJEVBiological
live attenuated Japanese encephalitis (JE) vaccine IMOJEV®
| Study group | Role | What they receive |
|---|---|---|
| Group 1 - Any status | Other | Up to 3-4 healthy adults Receives: Biological: IMOJEV |
| Group 2 - FlaviPrime Naive | Other | Up to 6-8 healthy adults who have never travelled to a flavivirus endemic area and are negative in screening tests for flavivirus immunity. Receives: Biological: IMOJEV |
| Group 3 - Flavivirus Exposed | Other | Up to 8-10 healthy adults who have had JE vaccine and/or are previously flavivirus exposed, either through receiving yellow fever vaccine up to 5 years before the study, or from being diagnosed with a flavivirus illness (e.g. dengue or Zika). Receives: Biological: IMOJEV |
What is being measured
The primary outcome is the main question the study is designed to answer.
Primary: Plasmablast Percentage of Total B Cells at 7 Days Post Vaccine
Plasmablast percentage of total B cells at 7 days post vaccine Number of plasmablasts sorted by flow cytometry at 7 days post vaccine
Measured: 1 week
Primary: Neutralisation Titre, Measured by 50% of Viral Plaque Reduction at One and Two Months Post Vaccine
Neutralising antibody titre, measured by 50% of viral plaque reduction at one and two months post vaccine
Measured: two months
Secondary outcomes (1)
Secondary: Number of Adverse Events Occurring in All Participants in One Month Post Vaccine
Number of adverse events occurring in all participants in one month post vaccine
Measured: one month
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted18 Apr 2019
- Study start16 Apr 2021
- Primary completion23 Dec 2021
- Study completion11 May 2022
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Other trials for Japanese EncephalitisStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase N/A
- Primary purpose
- Diagnosis
- Allocation
- Non-randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Enrolment
- 19 participants (actual)
Sponsor and investigators
- Lead sponsor
- University of Liverpool
- Sponsor type
- University, hospital or other
- Responsible party
- Principal investigator, Dr Lance Turtle, University of Liverpool
- Investigators
- Lance Turtle, Dr, Principal investigator, University of Liverpool
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT03920111
- Sponsor's protocol ID
- UoL001462 - 4833
- Acronym
- FlaviPrime
- Status last verified
- Jan 2025
- First submitted
- 4 Apr 2019
- Last updated
- 31 Jan 2025
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- No
Study at a glance
From the registry record, last updated by the sponsor on 31 Jan 2025. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Flavivirus Cross-priming Potential of Live Attenuated Japanese Encephalitis (JE) Vaccine IMOJEV in Flavivirus naïve and Flavivirus Experienced Participants
- ClinicalTrials.gov ID
- NCT03920111
- Acronym / sponsor ID
- FlaviPrime / UoL001462 - 4833
- Conditions
- Japanese Encephalitis
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 19 participants (actual)
- Lead sponsor
- University of LiverpoolUniversity, hospital or other
- Study start
- 16 Apr 2021 (actual)
- Primary completion
- 23 Dec 2021 (actual)
- Study completion
- 11 May 2022 (actual)
- First posted
- 18 Apr 2019 (actual)
- Results
- Posted 31 Jan 2025
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
There is a pressing need for a better experimental system to understand flavivirus antibody responses, beyond dengue, to make sure the investigators are using current vaccines to greatest effect and to inform the development of next-generation vaccines. This study will use live chimeric JE vaccine IMOJEV® as a tool for flavivirus epitope discovery. This will allow experimental JEV infection using replication competent, live, attenuated virus as a model, in a setting where the flavivirus infection history of humans can be tightly controlled.
Detailed description
This study will test the hypothesis that in previously flavivirus-exposed individuals, the antibody response is more broadly cross neutralising, and that this will lead to the identification of conserved virion surface epitopes that could be the target of second generation vaccines.
Exploratory Primary Objectives/Specific aims:
- To establish a human model system of JEV infection in healthy adult volunteers using live attenuated JE vaccine IMOJEV®.
- To sort and sequence individual responding B cells (plasmablasts) after vaccination with IMOJEV®, and to generate human monoclonal antibodies to JEV.
- To generate JEV specific human monoclonal antibodies from the sequences derived in (2).
- To describe the development, specificity, cross-reactivity and function of the T cell response to IMOJEV®.
- To establish a sample bank for future work on cross-reactive and other responses to flaviviruses, flavivirus vaccines and other emergent viruses.
Exploratory Secondary Objectives:
- To examine the specificity and cross-reactivity of the antibody response after JE vaccination, using serum and human monoclonal antibodies.
- To determine whether there are epitopes which can serve as the target of broadly cross-neutralising antibody responses.
Experimentally the fine specificity and cross-reactivity of the antibody response will be studied by cloning antibodies from plasmablasts (B cells responding to the vaccine) that have been single cell sorted by flow cytometry then sequenced at one week post vaccine. These human monoclonal antibodies will then be mapped on to the surface of the virus particle using established approaches, and tested to look for cross-reactive antibodies. T cell responses to the vaccine will be studied using custom pools of synthetic peptides by ELISpot and flow cytometry.
Study design
- Primary purpose
- Diagnosis
- Allocation
- Non-randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 3
| Arm | Type | Receives |
|---|---|---|
| Group 1 - Any status | Other | Biological: IMOJEVUp to 3-4 healthy adults |
| Group 2 - FlaviPrime Naive | Other | Biological: IMOJEVUp to 6-8 healthy adults who have never travelled to a flavivirus endemic area and are negative in screening tests for flavivirus immunity. |
| Group 3 - Flavivirus Exposed | Other | Biological: IMOJEVUp to 8-10 healthy adults who have had JE vaccine and/or are previously flavivirus exposed, either through receiving yellow fever vaccine up to 5 years before the study, or from being diagnosed with a flavivirus illness (e.g. dengue or Zika). |
Who may qualify
- Ages
- 18 to 70 years
- Sex
- All
- Healthy volunteers
- Accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (6 listed)
- A male or female adult between 18 and 70 years of age at consent.
- Written and informed consent obtained from participant and agreement of participant to comply with the requirements of the study
- Able to attend regularly to donate study blood samples for the duration of the study (8 weeks), no planned re-location or travel to a flavivirus endemic area during the study period.
- Satisfactory medical screen, as demonstrated by study screening document normal physical examination and normal screening blood tests
- Group 1: Any flavivirus exposure status; Group 2: No previous flavivirus vaccination (JE, tick borne encephalitis or yellow fever (YF)), no residence in a flavivirus endemic area nor planned travel to a flavivirus endemic area during the period of the study; Group 3: JE vaccine and/or yellow fever vaccine or other proven flavivirus infection within the last 10 years or other proven flavivirus infection (lifetime).
Key exclusion criteria (19 listed)
- Use of any investigational or non-registered drug within 5 half-lives of the drug, or 30 days preceding administration of study JE vaccine, whichever is longer; or planned use during the study period.
- Receipt of any investigational biologic agents with mechanisms of action that might affect the immune system, at the discretion of the CI and local PI.
- 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.
- Any confirmed or suspected immunosuppressive or immunodeficient condition.
- A family history of congenital or hereditary immunodeficiency.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| IMOJEVlive attenuated Japanese encephalitis (JE) vaccine IMOJEV® | Biological | Group 1 - Any status, Group 2 - FlaviPrime Naive, Group 3 - Flavivirus Exposed |
Primary outcome
Primary: Plasmablast Percentage of Total B Cells at 7 Days Post Vaccine
Time frame: 1 week
Plasmablast percentage of total B cells at 7 days post vaccine Number of plasmablasts sorted by flow cytometry at 7 days post vaccine
Primary: Neutralisation Titre, Measured by 50% of Viral Plaque Reduction at One and Two Months Post Vaccine
Time frame: two months
Neutralising antibody titre, measured by 50% of viral plaque reduction at one and two months post vaccine
1 secondary outcome
Secondary: Number of Adverse Events Occurring in All Participants in One Month Post Vaccine
Time frame: one month
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 31 Jan 2025.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Individual participant dataSharing planned: No
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Lance Turtle, Dr principal investigator
University of Liverpool
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A study testing IMOJEV in people with Japanese Encephalitis, run by University of Liverpool at 1 site in United Kingdom.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 6 inclusion and 19 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 31 Jan 2025. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in United Kingdom. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
Are results available for this study?
Yes. Results are posted in the registry (first posted 31 Jan 2025). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Primary: Plasmablast Percentage of Total B Cells at 7 Days Post Vaccine (time frame: 1 week). The study lists 2 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 31 Jan 2025.