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; Rafick Pierre Sékaly

doi:10.1038/ncomms10369

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, Rafick Pierre Sékaly^*

^*Corresponding author for this work

Medicine, Allergy Division

Research output: Contribution to journal › Article › peer-review

141 Scopus citations

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 curveâ ‰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.

Original language	English (US)
Article number	10369
Journal	Nature communications
Volume	7
DOIs	https://doi.org/10.1038/ncomms10369
State	Published - Jan 8 2016

Funding

We thank Giuseppe Del Giudice (Novartis Vaccines), Neil Greenspan (CWRU), Glenda Canderan (CWRU) for comments on the paper. ImmuneCarta acted as a central laboratory generating the Immune monitoring data presented in this study. ImmuneCarta was responsible for developing and validating the FCM panels and ELISAs for the quantitation of HBV, Cholera, Diphtheria, Tetanus and CMV antibody titres. Merck & Co. Inc. sponsored the study, funded clinical and laboratory activities, and performed the mRNA extraction and profiling. Grants by the FNIH (CTVIMC2) also supported this work.

ASJC Scopus subject areas

General Chemistry
General Biochemistry, Genetics and Molecular Biology
General Physics and Astronomy

UN SDGs

This output contributes to the following UN Sustainable Development Goals (SDGs)

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10.1038/ncomms10369

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Fourati, S., Cristescu, R., Loboda, A., Talla, A., Filali, A., Railkar, R., Schaeffer, A. K., Favre, D., Gagnon, D., Peretz, Y., Wang, I. M., Beals, C. R., Casimiro, D. R., Carayannopoulos, L. N., & Sékaly, R. P. (2016). Pre-vaccination inflammation and B-cell signalling predict age-related hyporesponse to hepatitis B vaccination. Nature communications, 7, Article 10369. https://doi.org/10.1038/ncomms10369

@article{be96d03f41cb459cb5e3a088dfd7f012,

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{\^a} ‰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.",

author = "Slim Fourati and Razvan Cristescu and Andrey Loboda and Aarthi Talla and Ali Filali and Radha Railkar and Schaeffer, {Andrea K.} and David Favre and Dominic Gagnon and Yoav Peretz and Wang, {I. Ming} and Beals, {Chan R.} and Casimiro, {Danilo R.} and Carayannopoulos, {Leonidas N.} and S{\'e}kaly, {Rafick Pierre}",

note = "Funding Information: We thank Giuseppe Del Giudice (Novartis Vaccines), Neil Greenspan (CWRU), Glenda Canderan (CWRU) for comments on the paper. ImmuneCarta acted as a central laboratory generating the Immune monitoring data presented in this study. ImmuneCarta was responsible for developing and validating the FCM panels and ELISAs for the quantitation of HBV, Cholera, Diphtheria, Tetanus and CMV antibody titres. Merck & Co. Inc. sponsored the study, funded clinical and laboratory activities, and performed the mRNA extraction and profiling. Grants by the FNIH (CTVIMC2) also supported this work.",

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Fourati, S, Cristescu, R, Loboda, A, Talla, A, Filali, A, Railkar, R, Schaeffer, AK, Favre, D, Gagnon, D, Peretz, Y, Wang, IM, Beals, CR, Casimiro, DR, Carayannopoulos, LN & Sékaly, RP 2016, 'Pre-vaccination inflammation and B-cell signalling predict age-related hyporesponse to hepatitis B vaccination', Nature communications, vol. 7, 10369. https://doi.org/10.1038/ncomms10369

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AU - Fourati, Slim

AU - Cristescu, Razvan

AU - Loboda, Andrey

AU - Talla, Aarthi

AU - Filali, Ali

AU - Railkar, Radha

AU - Schaeffer, Andrea K.

AU - Favre, David

AU - Gagnon, Dominic

AU - Peretz, Yoav

AU - Wang, I. Ming

AU - Beals, Chan R.

AU - Casimiro, Danilo R.

AU - Carayannopoulos, Leonidas N.

AU - Sékaly, Rafick Pierre

N1 - Funding Information: We thank Giuseppe Del Giudice (Novartis Vaccines), Neil Greenspan (CWRU), Glenda Canderan (CWRU) for comments on the paper. ImmuneCarta acted as a central laboratory generating the Immune monitoring data presented in this study. ImmuneCarta was responsible for developing and validating the FCM panels and ELISAs for the quantitation of HBV, Cholera, Diphtheria, Tetanus and CMV antibody titres. Merck & Co. Inc. sponsored the study, funded clinical and laboratory activities, and performed the mRNA extraction and profiling. Grants by the FNIH (CTVIMC2) also supported this work.

PY - 2016/1/8

Y1 - 2016/1/8

N2 - 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 curveâ ‰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.

AB - 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 curveâ ‰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.

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

Abstract

Funding

ASJC Scopus subject areas

UN SDGs

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