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

Abstract

Several studies have shown that the pre-vaccination immune state is associated with the antibody response to vaccination. However, the generalizability and mechanisms that underlie this association remain poorly defined. Here, we sought to identify a common pre-vaccination signature and mechanisms that could predict the immune response across 13 different vaccines. Analysis of blood transcriptional profiles across studies revealed three distinct pre-vaccination endotypes, characterized by the differential expression of genes associated with a pro-inflammatory response, cell proliferation, and metabolism alterations. Importantly, individuals whose pre-vaccination endotype was enriched in pro-inflammatory response genes known to be downstream of nuclear factor-kappa B showed significantly higher serum antibody responses 1 month after vaccination. This pro-inflammatory pre-vaccination endotype showed gene expression characteristic of the innate activation state triggered by Toll-like receptor ligands or adjuvants. These results demonstrate that wide variations in the transcriptional state of the immune system in humans can be a key determinant of responsiveness to vaccination.

Immune signature atlas of vaccines: learning from the good responders

“…Overall, Fourati et al 2 and Hagan et al 4 have demonstrated the use of this compendium as a highly valuable tool to gain insight into the variation in antibody response observed between individuals, which provides an excellent resource for immunologists and vaccinologists to use in comparative studies to obtain further mechanistic insight into the effect of genetic factors (age, sex, ethnicity) and environmental factors (nutrition, geographical location, time of vaccination) that shape cellular and molecular mechanisms and underpin antibody responsiveness. Growing evidence points to adult females having better protective immune responses 9 , possibly due to increased innate immune responses; to pregnant women responding better to vaccination in the first and third trimesters; 10 to novel mRNA vaccines inducing a more potent monocyte response; 11 and to greater effectiveness of vaccination in the morning because of circadian rhythms 12 .…”

“…Using unsupervised clustering analysis of blood transcriptional modules previously coupled to immunological function 1 , Fourati et al classified pre-vaccination transcriptional profiles into three main endotypes 2 . Contributing to 12% of the variance observed in healthy participants, these endotypes were differentially defined by the expression of blood modules associated with innate immune responses, including Toll-like receptor (TLR) genes, interferon-mediated genes and genes associated with metabolic alterations downstream of the transcription factor NF-κB, that were critical for antiviral responses, antigen presentation and B cell activation.…”

Multiscale integration of human and single-cell variations reveals unadjuvanted vaccine high responders are naturally adjuvanted

“…Such studies have used unbiased immune profiling to identify signatures of response to perturbations and predictors of outcomes such as antibody response to vaccination [6][7][8][9][10][11][12][13][14] , uncovering contributions from intrinsic factors, such as genetics 15 , age 16,17 , and sex 18 . Furthermore, accumulating evidence from these studies supports the hypothesis that immune system status prior to a perturbation can predict and potentially influence both response quality and quantity 6,16,[19][20][21][22][23] . For example, we identified transcriptome signatures reflective of an immune system "set point" predictive of higher antibody response following vaccination in healthy individuals 22 ; the same signature when evaluated during relative clinical quiescence was also linked to increased plasma cell related transcriptomic activity during disease flares in lupus patients.…”

Baseline innate and T cell populations are correlates of protection against symptomatic influenza virus infection independent of serology

“…Further complicating the study of correlates of protection against influenza is the substantial degree of baseline immune variation that exists across humans, which is now recognized as a key determinant in predicting efficacy of some vaccines and therapeutics, and modeling disease outcomes [14][15][16][17][18] . Differences in host genetics, environmental and demographic factors, and antigen exposure histories impact the composition of baseline innate, cellular, and humoral compartments, and may augment differing responses to influenza virus infection or vaccination 17,[19][20][21][22][23][24][25][26][27][28][29][30] .…”