Systems Analysis of Immunity to Influenza Vaccination across Multiple Years and in Diverse Populations Reveals Shared Molecular Signatures

Abstract

SUMMARY Systems approaches have been used to describe molecular signatures driving immunity to influenza vaccination in humans. Whether such signatures are similar across multiple seasons and in diverse populations is unknown. We applied systems approaches to study immune responses in young, elderly, and diabetic subjects vaccinated with the seasonal influenza vaccine across five consecutive seasons. Signatures of innate immunity and plasmablasts correlated with and predicted influenza antibody titers at 1 month after vaccination with >80% accuracy across multiple seasons but were not associated with the longevity of the response. Baseline signatures of lymphocyte and monocyte inflammation were positively and negatively correlated, respectively, with antibody responses at 1 month. Finally, integrative analysis of microRNAs and transcriptomic profiling revealed potential regulators of vaccine immunity. These results identify shared vaccine-induced signatures across multiple seasons and in diverse populations and might help guide the development of next-generation vaccines that provide persistent immunity against influenza.

Reevaluation of immune activation in the era of cART and an aging HIV-infected population

“…The prevalence of existing humoral immune responses in the human population complicates use of the influenza vaccination model for determining immunological predictors of vaccine responsiveness. Nevertheless, many groups have used and continue to use the seasonal flu vaccine to probe immune competence and explore new biomarkers in order to improve vaccine design (29,(37)(38)(39)(40)(41)(42)(43). The use herein of absolute response and response score criteria facilitates comparisons without altering the conventional definitions for determining vaccine responder status.…”

Exploring the Limitations of Peripheral Blood Transcriptional Biomarkers in Predicting Influenza Vaccine Responsiveness

“…Specifically, we used the testing cohort described in Nakaya et al [11], which is related to the TIV vaccination campaigns of 2009, 2010, and 2011 (set #3). The testing cohort includes 21 subjects out of a total of 212, selected because only for them the classification in high/low responders was available.…”

“…Recently, several studies [8][9][10][11] have analyzed the transcriptome profile of peripheral blood, or blood-derived cells, to study immunity to the trivalent influenza vaccine (TIV) in humans. These studies decoded the global pattern of transcriptional response to TIV vaccination and independently reported that the extent of upregulation of a set of interferoninducible genes, one to three days after vaccination, and of genes involved in plasmablasts differentiation and activity, seven days after vaccination, correlates with the magnitude of serum functional antibody titers measured after one month.…”

“…These studies decoded the global pattern of transcriptional response to TIV vaccination and independently reported that the extent of upregulation of a set of interferoninducible genes, one to three days after vaccination, and of genes involved in plasmablasts differentiation and activity, seven days after vaccination, correlates with the magnitude of serum functional antibody titers measured after one month. Among those, Nakaya and colleagues [10,11] extended this further, by applying a machine learning algorithm to identify sets of genes that could predict subjects' seroresponse across independent TIV vaccination trials.…”

Vaccinology in the era of high-throughput biology

“…In our work, in collaboration with Advanced Immunization Technologies, we are identifying early signatures of TIV immunogenicity in children of less than 2 years of age [61]. Additionally, we performed a comprehensive set of immunological and high-throughput analyses on elderly populations (more than 65 years old), including microRNA and gene expression profiling, to assess the mechanisms of immunosenescent responses to TIV and to verify if the signatures that predict antibody responses in young adults [7] can also be used to predict elderly responses [61]. These studies (figure 5) may offer new insights about efficacy of TIV in people at extremes of age and provide useful information for the rational design of novel vaccines or strategies that target these populations.…”