Transcriptional atlas of the human immune response to 13 vaccines reveals a common predictor of vaccine-induced antibody responses

Abstract

Systems biology approaches have been used to define molecular signatures and mechanisms of immunity to vaccination. However, most such studies have been done with single vaccines, and comparative analysis of the response to different vaccines is lacking. We integrated temporal transcriptional data of over 3,000 samples, obtained from 820 healthy adults across 28 studies of 13 different vaccines and analyzed vaccination-induced signatures associated with the antibody response. Most vaccines induced similar kinetics of shared transcriptional signatures, including signatures of innate immunity occurring 1-3 days post-vaccination, as well as the canonical plasmablast and cell cycle signatures appearing 7 days post-vaccination. However, the yellow fever vaccine YF-17D uniquely induced an early transient signature of T and B cell activation at Day 1, followed by delayed antiviral/interferon and plasmablast signatures that peaked at Days 7 and 14-21, respectively. Thus, despite the shared transcriptional response to most vaccines, at any given time point there was no evidence for a “universal signature” that could be used to predict the antibody response to all vaccines. However, accounting for the asynchronous nature of responses led to the identification of a time-adjusted signature that improved prediction antibody of responses across vaccines. These results provide a transcriptional atlas of the human immune response to vaccination and define a common, time-adjusted signature of antibody responses to vaccination.

Pan-vaccine analysis reveals innate immune endotypes predictive of antibody responses to vaccination

“…In contrast, the global classifier of vaccine responses identified herein performed as well as a classifier trained on any given vaccine and tested on that same vaccine. A similar finding is described in our companion paper by Hagan et al 31 that focuses on post-vaccination response to the same 13 vaccines and identified a global transcriptomic signature associated with antibody response when all the vaccines are synchronized before building a classifier.…”

Early B cell transcriptomic markers of measles-specific humoral immunity following a 3rd dose of MMR vaccine

“…The early transcriptional events in B cells upon antigenic stimulation are of critical importance for the generation and maintenance of humoral immunity. Since other studies have reported associations between plasmablast transcriptional response (peaking at Day 7-8) and antibody titers following vaccination, our study sought to identify early (Day 8, plasmablast) transcriptional signatures in B cells that are highly correlated with vaccine-induced humoral immune outcomes ( 24 – 27 ). To achieve this, we fit linear models for each gene with the Day 8 gene expression as the covariate.…”

Host Functional Response to a Prototypic Orally Delivered Self-Replicating Vaccine Platform

“…How to relate these findings to vaccine-induced protection from infection and disease is unknown and reveals current limitations in the field of vaccinology. Identification of pre-and post-immunization immune profiles or transcriptional responses from blood with the goal of identifying profiles that correlate with optimal vaccine performance is being actively studied [28,36]. A recent publication evaluated 13 different vaccines and showed that a pre-vaccination pro-inflammatory endotype that included upregulation of genes encoding for pathogenassociated molecular patterns correlated with a better response to vaccination [28].…”

“…A recent publication evaluated 13 different vaccines and showed that a pre-vaccination pro-inflammatory endotype that included upregulation of genes encoding for pathogenassociated molecular patterns correlated with a better response to vaccination [28]. Post-vaccination gene expression from these same individuals identified vaccines that clustered into groups based on similar immune responses, even though there was a heterogenous response between these clusters [36]. Such studies show the possibility of systems vaccinology to identify pre-vaccination states and vaccination types or adjuvants that could perform better in individuals or populations depending on age, health status, or with previous or current pathogen exposure.…”