Abstract
Aging is associated with hyporesponse to vaccination, whose mechanisms remain unclear. In this study hepatitis B virus (HBV)-naive older adults received three vaccines, including one against HBV. Here we show, using transcriptional and cytometric profiling of whole blood collected before vaccination, that heightened expression of genes that augment B-cell responses and higher memory B-cell frequencies correlate with stronger responses to HBV vaccine. In contrast, higher levels of inflammatory response transcripts and increased frequencies of pro-inflammatory innate cells correlate with weaker responses to this vaccine. Increased numbers of erythrocytes and the haem-induced response also correlate with poor response to the HBV vaccine. A transcriptomics-based pre-vaccination predictor of response to HBV vaccine is built and validated in distinct sets of older adults. This moderately accurate (area under the curve≈65%) but robust signature is supported by flow cytometry and cytokine profiling. This study is the first that identifies baseline predictors and mechanisms of response to the HBV vaccine.
Highlights
Aging is associated with hyporesponse to vaccination, whose mechanisms remain unclear
We focused our analysis on the hepatitis B virus (HBV) vaccine response
Kernel density estimation of anti-HBsAg titres showed that a cutoff of 5 mIU ml À 1 demarcated study participants as HBV vaccine responders (Ab titresZ5 mIU ml À 1) and poor-responders (Ab titres below detection threshold) (Supplementary Fig. 1b)
Summary
Aging is associated with hyporesponse to vaccination, whose mechanisms remain unclear. A transcriptomics-based pre-vaccination predictor of response to HBV vaccine is built and validated in distinct sets of older adults. This moderately accurate (area under the curveE65%) but robust signature is supported by flow cytometry and cytokine profiling. The impracticality of sampling human lymphoid organs coupled with limited translatability of animal models[7] poses a formidable challenge to the discovery of these mechanisms as well as biomarkers of VHR using single-hypothesis approaches To overcome this challenge, high dimensionality studies of cellular and molecular responses to vaccines have been proposed to speed convergence to actionable mechanistic and biomarker hypotheses; an approach termed ‘systems vaccinology’[8]. Transcriptomics, polychromatic FCM and serum cytokine profiling were used to generate an integrated model to inform on potential involvement of specific cellular and molecular pathways in nascent anti-HBsAg responses in older adults
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