Flavivirus Cross-priming Potential of IMOJEV — FlaviPrime  

Japanese Encephalitis Clinical Trial

Official title: Flavivirus Cross-priming Potential of Live Attenuated Japanese Encephalitis (JE) Vaccine IMOJEV in Flavivirus naïve and Flavivirus Experienced Participants

Status Completed

Clinical 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. 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.

Clinical Trial 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. ;

Related Conditions & MeSH terms

• Encephalitis
• Encephalitis, Japanese
• Japanese Encephalitis

• NCT number: NCT03920111
• Study type: Interventional
• Source: University of Liverpool
• Status: Completed
• Phase: N/A
• Start date: April 16, 2021
• Completion date: May 11, 2022