CD4 T cell immune correlates of Zika virus exposure

Abstract

A feature common to the pathogenesis of flavivirus exposure in humans is the diversity of clinical outcomes. In the case of exposure to Zika virus, outcomes can range from asymptomatic exposure to fever, rash, joint pain, conjunctivitis, Guillain Barre syndrome and probably, neonatal microcephaly. Some regions of Brazil (including Sao Paulo where our study will be based) have witnessed a sharp peak of microcephaly reporting, and this has caused considerable alarm, including pregnant women seeking abortions and women being advised to avoid pregnancy. While host immunity to Zika virus is essentially uncharted territory, it may be possible to extrapolate some broad principles from studies of immunity to the most closely related arbovirus, West Nile virus (WNV). Eddie James and Bill Kwok, co-investigators on this proposal, have been arguably the world-leaders in characterizing T cell immune correlates of disease outcome in WNV exposure. Their studies have been centred on detailed characterization of T cell subsets and phenotypes through flow cytometric selection with HLA/peptide WNV tetramers - an approach that will here be applied to Zika. At a time when steps are being taken to roll-out of various Zika vaccine candidates (including the NIH-VRC candidate) and design protocols for their evaluation, our rationale is that it will be vital to have a clear grasp of T cell immune phenotypes associated with different disease outcomes, based on the premise that not all response phenotypes are beneficial and some may be explicitly pathogenic. This offers the opportunity to supply novel insights into Zika protection versus pathogenesis with the potential for direct impact through informing patient management. (AU)