Integrated transcriptomics and metabolomics profiling delineates early molecular correlates of immunity to herpes zoster vaccination in humans

The goal of this study is to characterize the human immune responses to the live attenuated Herpes zoster vaccine Zostavax, to understand the molecular and cellular mechanisms that lead to antibody production and T cell induction, and to understand the difference between young and elderly healthy adults. The overall data collection included antigen specific assays, flow cytometric profiling of innate and adaptive cell populations, measurement of serum cytokines, and transcriptomic and metabolomics signatures. Zostavax induced robust antigen-specific antibody responses, and significant T cell responses. A number of gene pathways were upregulated after vaccination. Using our previously developed blood transcription modules, we also identified transcriptomic correlates to antibody response. Furthermore, this study revealed strong association between PBMC transcriptomics and plasma metabolomics. Integrative analysis of orthogonal datasets from metabolomics, transcriptomic and immune profiling facilitated a temporal reconstruction of Zostavax induced biological networks culminating in antibody responses , and the delineation of novel molecular correlates of vaccine immunity. A longitudinal study of Zostavax® vaccination was conducted on healthy adults, between August 2011 and November 2013. Seventy-seven people were enrolled at Atlanta, Georgia and Denver, Colorado, USA. The cohort contained two age groups: 33 subjects considered to be young adults between the age of 25~40, and 44 subjects as elderly between the age of 60~79 years . The subject’s blood was collected at baseline, days 1, 3, 7, 14, 28, 90 and 180 post-vaccination. Throughout the course of study, we measured Zostavax specific antibody titers, B and T cell populations, as well as various cell populations involved in innate immunity, including dendritic cell (DC) and monocyte subsets. Cytokines were assayed by a 27-plex Luminex platform. Varicella zoster viremia was measured by real-time PCR and nested PCR reactions. We profiled transcriptomics of PBMCs, and high-resolution mass spectrometers to obtain metabolomics of plasma from subjects at baseline and on days 1-7 post-vaccination.