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

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 .…”

“…Hagan et al applied the same approach to find common and unique features associated with antibody responses across vaccines in the early post-vaccination period 4 . Unsupervised analysis of gene profiles revealed four temporal expression patterns: on days 1-3, innate responses (predominant in live viral vectors) and lower natural killer cell (NK cell) responses; and on day 7, expansion of plasmablasts and stimulation of CD4 + T cells.…”

“…Best studied is the effect of age on antibody responsiveness, with elderly individuals known to have lower antibody titers than younger people after vaccination 8 . Although Fourati et al did not address how age contributed to the primed endotype before vaccination 2 -possibly due to data scarcity in the datasets -Hagan et al used their dataset to compare blood modules after vaccination 4 . Consistent with previous results 8 , they found that elderly individuals had reduced transcriptional expression in modules associated with interferon responses and plasmablasts, but the kinetics of responses remained the same.…”

Tracking of activated cTfh cells following sequential influenza vaccinations reveals transcriptional profile of clonotypes driving a vaccine-induced immune response

“…Recent studies have aimed to identify such biomarkers in the form of a transcriptional atlas of the human immune response to several vaccinations (56,57). While such studies have identified features of a vaccine induced immune response, they were heterogeneous at both the individual and vaccine level (56,57). To combat this, Hagan et al (57) proposed the development of a 'vaccine chip' devised to monitor plasmablast signatures as a biomarker to predict protective immune responses in vaccine trials.…”

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] .…”