Characterisation of rapid onset protection after Nipah vaccination, and the influence of prior paramyxovirus exposure on reactivity to Nipah

This project aims to identify potential markers of rapid onset protection after ChAdOx1 NipahB vaccination, and evaluate the cross-reactivity of Nipah virus with circulating paramyxoviruses in Bangladesh. Neutralising antibodies (nAbs) are generally considered the main defence against Nipah infection. However, pre-clinical studies show vaccine-induced protection from lethal challenge within a week post-vaccination, before detectable nAbs. We will model the early immune response to ChAdOx1 NipahB in phase 1 trials in UK and Bangladesh, using systems immunology to identify a panel of markers of the early response which are applicable across populations and measured by robust and transferrable assays. Clinical trials and subsequent NHP challenge study to evaluate marker correlation with rapid protection from disease after vaccination are planned with and funded by CEPI. Immune responses to Nipah vaccination or infection may be influenced by previous exposure to related paramyxoviruses. In vitro, T-cell clones against conserved paramyxoviruses epitopes kill Nipah-infected cells, but the extent of cross-reactivity in vaccine target populations is unknown. We will identify relevant paramyxoviruses with a serosurvey across Bangladesh, then develop a T-cell reactivity assay differentiating species-specific and pan-paramyxovirus epitope responses. We can then evaluate the potential impact of T-cell cross- reactivity on responses to Nipah vaccination or infection.