Research ResourceVaccines

Transcriptional profiles of adjuvanted hepatitis B vaccines display variable interindividual homogeneity but a shared core signature

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Science Translational Medicine  11 Nov 2020:
Vol. 12, Issue 569, eaay8618
DOI: 10.1126/scitranslmed.aay8618

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Patterns of adjuvanticity

Understanding how adjuvants improve vaccine-induced immune responses is important for the development of successful vaccines. De Mot et al. performed transcriptome analysis on whole blood taken from the participants of a previously reported clinical study that trialed different adjuvants alongside hepatitis B vaccine antigen. Differential expression of a core gene signature related to innate immune response and natural killer cells correlated with the antibody response observed in vaccine recipients after two doses regardless of the adjuvant administered, suggesting that these responses are important for vaccine immunogenicity.

Abstract

The current routine use of adjuvants in human vaccines provides a strong incentive to increase our understanding of how adjuvants differ in their ability to stimulate innate immunity and consequently enhance vaccine immunogenicity. Here, we evaluated gene expression profiles in cells from whole blood elicited in naive subjects receiving the hepatitis B surface antigen formulated with different adjuvants. We identified a core innate gene signature emerging 1 day after the second vaccination and that was shared by the recipients of vaccines formulated with adjuvant systems AS01B, AS01E, or AS03. This core signature associated with the magnitude of the hepatitis B surface-specific antibody response and was characterized by positive regulation of genes associated with interferon-related responses or the innate cell compartment and by negative regulation of natural killer cell–associated genes. Analysis at the individual subject level revealed that the higher immunogenicity of AS01B-adjuvanted vaccine was linked to its ability to induce this signature in most vaccinees even after the first vaccination. Therefore, our data suggest that adjuvanticity is not strictly defined by the nature of the receptors or signaling pathways it activates but by the ability of the adjuvant to consistently induce a core inflammatory signature across individuals.

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