As part of WP2 a comprehensive survey of B and T cell immunity of trial participants as well as identification of the primary correlates of protection will be conducted. The work is organised around six objectives:
1. Functional characterisation of vaccine induced antibodies to determine the magnitude and quality of neutralising activity.
2. Assessment of cross neutralising capacity of vaccine induced antibodies against a panel of alphaviruses.
3. Evaluation of T cell–mediated responses, including cytokine profiles and cellular phenotypes.
4. Structural characterisation of vaccine induced polyclonal antibodies in complex with different alphaviruses to map key immunogenic epitopes, and to relate epitope footprints to neutralisation and cross reactivity.
5. Determination of the risk of antibody dependent enhancement (ADE) in vaccinated individuals.
6. Transcriptomic profiling of samples from vaccinated individuals using single cell RNA sequencing (scRNA seq) to identify molecular signatures, pathways, and immune responses associated with vaccination.
Together, these analyses aim to define the immunological features most closely linked to protection and durability, informing rational vaccine development and policy.