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.
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.
Study Type
INTERVENTIONAL
Allocation
NON_RANDOMIZED
Purpose
DIAGNOSTIC
Masking
NONE
Enrollment
19
live attenuated Japanese encephalitis (JE) vaccine IMOJEV®
Liverpool University Hospitals NHS Foundation Trust
Liverpool, United Kingdom
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
Time frame: 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
Time frame: two months
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
Time frame: one month
This platform is for informational purposes only and does not constitute medical advice. Always consult a qualified healthcare professional.