title: Pre-vaccination inflammation and B-cell signalling predict age-related hyporesponse to hepatitis B vaccination.
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.
authors.affiliation: Vaccine and Gene Therapy Institute of Florida, Port St Lucie, Florida 34987, USA.|Department of Pathology, University Hospitals of Cleveland and Case Western Reserve University, 2103 Cornell Road, Cleveland, Ohio 44106, USA.
authors.forename: Slim
authors.identifier: http://orcid.org/0000-0001-6609-7587
authors.initials: S
authors.lastname: Fourati
authors.affiliation: Department of Discovery Medicine, Merck Research Laboratories, Rahway, New Jersey 07065, USA.
authors.forename: Razvan
authors.initials: R
authors.lastname: Cristescu
authors.affiliation: Department of Discovery Medicine, Merck Research Laboratories, Rahway, New Jersey 07065, USA.
authors.forename: Andrey
authors.initials: A
authors.lastname: Loboda
authors.affiliation: Vaccine and Gene Therapy Institute of Florida, Port St Lucie, Florida 34987, USA.|Department of Pathology, University Hospitals of Cleveland and Case Western Reserve University, 2103 Cornell Road, Cleveland, Ohio 44106, USA.
authors.forename: Aarthi
authors.initials: A
authors.lastname: Talla
authors.affiliation: Vaccine and Gene Therapy Institute of Florida, Port St Lucie, Florida 34987, USA.|Department of Pathology, University Hospitals of Cleveland and Case Western Reserve University, 2103 Cornell Road, Cleveland, Ohio 44106, USA.
authors.forename: Ali
authors.initials: A
authors.lastname: Filali
authors.affiliation: Department of Discovery Medicine, Merck Research Laboratories, Rahway, New Jersey 07065, USA.
authors.forename: Radha
authors.initials: R
authors.lastname: Railkar
authors.affiliation: Department of Discovery Medicine, Merck Research Laboratories, Rahway, New Jersey 07065, USA.
authors.forename: Andrea K
authors.initials: AK
authors.lastname: Schaeffer
authors.affiliation: Caprion/ImmuneCarta, Montréal, Québec, Canada H1W 4A4.
authors.forename: David
authors.initials: D
authors.lastname: Favre
authors.affiliation: Caprion/ImmuneCarta, Montréal, Québec, Canada H1W 4A4.
authors.forename: Dominic
authors.initials: D
authors.lastname: Gagnon
authors.affiliation: Caprion/ImmuneCarta, Montréal, Québec, Canada H1W 4A4.
authors.forename: Yoav
authors.initials: Y
authors.lastname: Peretz
authors.affiliation: Department of Discovery Medicine, Merck Research Laboratories, Rahway, New Jersey 07065, USA.
authors.forename: I-Ming
authors.initials: IM
authors.lastname: Wang
authors.affiliation: Department of Discovery Medicine, Merck Research Laboratories, Rahway, New Jersey 07065, USA.
authors.forename: Chan R
authors.initials: CR
authors.lastname: Beals
authors.affiliation: Department of Discovery Medicine, Merck Research Laboratories, Rahway, New Jersey 07065, USA.
authors.forename: Danilo R
authors.initials: DR
authors.lastname: Casimiro
authors.affiliation: Department of Discovery Medicine, Merck Research Laboratories, Rahway, New Jersey 07065, USA.
authors.forename: Leonidas N
authors.initials: LN
authors.lastname: Carayannopoulos
authors.affiliation: Vaccine and Gene Therapy Institute of Florida, Port St Lucie, Florida 34987, USA.|Department of Pathology, University Hospitals of Cleveland and Case Western Reserve University, 2103 Cornell Road, Cleveland, Ohio 44106, USA.
authors.forename: Rafick-Pierre
authors.initials: RP
authors.lastname: Sékaly
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000375:Aging / Q000276:immunology* / Q000378:metabolism; D001402:B-Lymphocytes / Q000502:physiology*; D015415:Biomarkers / Q000097:blood; D015331:Cohort Studies; D004906:Erythrocyte Count; D005260:Female; D005434:Flow Cytometry; D006514:Hepatitis B Surface Antigens / Q000276:immunology*; D017325:Hepatitis B Vaccines / Q000276:immunology*; D006801:Humans; D007249:Inflammation / Q000378:metabolism*; D008297:Male; D008875:Middle Aged; D059467:Transcriptome; D014611:Vaccination
chemical_list: D015415:Biomarkers; D006514:Hepatitis B Surface Antigens; D017325:Hepatitis B Vaccines