Further studies: CD4 T cell immune correlates of Zika virus exposure

Abstract

Current knowledge of T cell immunity to Zika virus is minimal. For a disease of such diverse outcomes, from asymptomatic exposure to Guilain-Barre syndrome or neonatal microcephaly, there is a pressing need to characterize immunity so as to comprehend the difference between protective and pathogenic T cell responses. In West Nile virus (WNV) infection, for example, neuropathgenic complications are themselves attributed to effects of T cells. We seek to supply the Zika research community with the first detailed dataset of CD4 T cell immunity to Zika virus, establishing the immune correlates of differential disease outcomes after exposure. Our expertise and track record in this regard is based in 12 years funding to the Altmann/Boyton and Kwok/James teams within the consortia of the NIH Epitope Discovery Program. This has been a programme of high-throughput analysis to achieve rapid characterisation of immunity in response to emerging pathogens. As such, the teams are ready to go with precisely the toolkit required for the proposed study. Kwok/James have led the way in characterisation of protective/pathogenic flavivirus immune correlates, generating tetramers for multiple HLA alleles. The London and Seattle labs will here team with Silva's lab in Sao Paulo. Patients will be characterized, covering phenotypes from mild to severe, and CD4 T cell immunity analyzed against ENV, NS5, NS3, and NS1. This will encompass qualitative and quantitative aspects by ELIsoot and HLA/Zika tetramer flow cytometry. (AU)