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Flavivirus Cross-priming Potential of IMOJEV (FlaviPrime)

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Know the risks and potential benefits of clinical studies and talk to your health care provider before participating. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT03920111
Recruitment Status : Not yet recruiting
First Posted : April 18, 2019
Last Update Posted : November 13, 2020
Sponsor:
Information provided by (Responsible Party):
Dr Lance Turtle, University of Liverpool

Brief 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. 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.

Condition or disease Intervention/treatment Phase
Japanese Encephalitis Biological: IMOJEV Not Applicable

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:

  1. To establish a human model system of JEV infection in healthy adult volunteers using live attenuated JE vaccine IMOJEV®.
  2. To sort and sequence individual responding B cells (plasmablasts) after vaccination with IMOJEV®, and to generate human monoclonal antibodies to JEV.
  3. To generate JEV specific human monoclonal antibodies from the sequences derived in (2).
  4. To describe the development, specificity, cross-reactivity and function of the T cell response to IMOJEV®.
  5. 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:

  1. To examine the specificity and cross-reactivity of the antibody response after JE vaccination, using serum and human monoclonal antibodies.
  2. 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.

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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 20 participants
Allocation: Non-Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)
Primary Purpose: Diagnostic
Official Title: Flavivirus Cross-priming Potential of Live Attenuated Japanese Encephalitis (JE) Vaccine IMOJEV in Flavivirus naïve and Flavivirus Experienced Participants
Estimated Study Start Date : January 18, 2021
Estimated Primary Completion Date : May 31, 2021
Estimated Study Completion Date : July 31, 2021


Arm Intervention/treatment
Group 1 - Any status
Up to 3-4 healthy adults
Biological: IMOJEV
live attenuated Japanese encephalitis (JE) vaccine IMOJEV®

Group 2 - FlaviPrime Naive
Up to 6-8 healthy adults who have never travelled to a flavivirus endemic area and are negative in screening tests for flavivirus immunity.
Biological: IMOJEV
live attenuated Japanese encephalitis (JE) vaccine IMOJEV®

Group 3 - Flavivirus Exposed
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).
Biological: IMOJEV
live attenuated Japanese encephalitis (JE) vaccine IMOJEV®




Primary Outcome Measures :
  1. 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

  2. Primary: Neutralising antibody 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


Secondary Outcome Measures :
  1. Secondary: Number of adverse events occurring in all participants in one month post vaccine [ Time Frame: one month ]
    Number of adverse events occurring in all participants in one month post vaccine



Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.


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Ages Eligible for Study:   18 Years to 70 Years   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   Yes
Criteria

Inclusion Criteria:

  1. A male or female adult between 18 and 70 years of age at consent.
  2. Written and informed consent obtained from participant and agreement of participant to comply with the requirements of the study
  3. 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.
  4. Satisfactory medical screen, as demonstrated by study screening document normal physical examination and normal screening blood tests
  5. 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).
  6. An efficacious method of contraception must be used during the study for women of childbearing potential.

Exclusion Criteria:

  1. 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.
  2. 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.
  3. 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.
  4. Any confirmed or suspected immunosuppressive or immunodeficient condition.
  5. A family history of congenital or hereditary immunodeficiency.
  6. 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.
  7. 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.
  8. History of having received JE vaccine, yellow fever vaccine, tick-borne encephalitis vaccine or experimental flavivirus vaccine (group 2 only).
  9. Detectable anti Flavivirus neutralizing antibodies in screening tests (group 2 only).
  10. 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.
  11. 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.
  12. Presence of any inflammatory condition that might require immunomodulatory therapy.
  13. 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).
  14. Current or previous abattoir worker or sheep farmer in Scotland (risk of Louping ill virus exposure; group 2 only).
  15. Administration of immunoglobulins and/or any blood products within the three months preceding administration of vaccine, or planned administration during the study period.
  16. Seropositive for HIV.
  17. Pregnancy or Lactation.
  18. History of excessive alcohol consumption (>28 units per week), drug abuse or significant psychiatric illness.
  19. 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).

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT03920111


Contacts
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Contact: Lance Turtle, Dr 01517957554 Lance.Turtle@liverpool.ac.uk
Contact: Priya Francis 01517949766 FlaviPrime@liverpool.ac.uk

Sponsors and Collaborators
University of Liverpool
Investigators
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Principal Investigator: Lance Turtle, Dr University of Liverpool
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Responsible Party: Dr Lance Turtle, Senior Clinical Lecturer, University of Liverpool
ClinicalTrials.gov Identifier: NCT03920111    
Other Study ID Numbers: UoL001462 - 4833
First Posted: April 18, 2019    Key Record Dates
Last Update Posted: November 13, 2020
Last Verified: November 2020
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No

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Studies a U.S. FDA-regulated Drug Product: No
Studies a U.S. FDA-regulated Device Product: No
Additional relevant MeSH terms:
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Encephalitis, Japanese
Encephalitis
Brain Diseases
Central Nervous System Diseases
Nervous System Diseases
Encephalitis, Arbovirus
Arbovirus Infections
Virus Diseases
Encephalitis, Viral
Central Nervous System Viral Diseases
RNA Virus Infections
Flavivirus Infections
Flaviviridae Infections
Infectious Encephalitis
Central Nervous System Infections