Pre-vaccination inflammation and B-cell signalling predict age-related hyporesponse to hepatitis B vaccination

Slim Fourati, Razvan Cristescu, Andrey Loboda, Aarthi Talla, Ali Filali, Radha Railkar, Andrea K. Schaeffer, David Favre, Dominic Gagnon, Yoav Peretz, I-Ming Wang, Chan R. Beals, Danilo R. Casimiro, Leonidas N. Carayannopoulos and Rafick-Pierre Sékaly ()
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Slim Fourati: Vaccine and Gene Therapy Institute of Florida
Razvan Cristescu: Merck Research Laboratories
Andrey Loboda: Merck Research Laboratories
Aarthi Talla: Vaccine and Gene Therapy Institute of Florida
Ali Filali: Vaccine and Gene Therapy Institute of Florida
Radha Railkar: Merck Research Laboratories
Andrea K. Schaeffer: Merck Research Laboratories
David Favre: Caprion/ImmuneCarta
Dominic Gagnon: Caprion/ImmuneCarta
Yoav Peretz: Caprion/ImmuneCarta
I-Ming Wang: Merck Research Laboratories
Chan R. Beals: Merck Research Laboratories
Danilo R. Casimiro: Merck Research Laboratories
Leonidas N. Carayannopoulos: Merck Research Laboratories
Rafick-Pierre Sékaly: Vaccine and Gene Therapy Institute of Florida

Nature Communications, 2016, vol. 7, issue 1, 1-12

Abstract: 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.

Date: 2016
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DOI: 10.1038/ncomms10369

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