Esther Bartholomeus1, Nicolas De Neuter2, Pieter Meysman2, Arvid Suls1, Nina Keersmaekers3, George Elias4, Hilde Jansens5, Niel Hens6, Evelien Smits7, Viggo Van Tendeloo4, Philippe Beutels3, Pierre Van Damme8, Benson Ogunjimi9, Kris Laukens2, Geert Mortier10. 1. Department of Medical Genetics, University of Antwerp/Antwerp University Hospital, Edegem, Belgium; AUDACIS, Antwerp Unit for Data Analysis and Computation in Immunology and Sequencing, University of Antwerp, Antwerp, Belgium. 2. AUDACIS, Antwerp Unit for Data Analysis and Computation in Immunology and Sequencing, University of Antwerp, Antwerp, Belgium; Adrem Data Lab, Department of Mathematics and Computer Science, University of Antwerp, Antwerp, Belgium; Biomedical Informatics Research Network Antwerp (biomina), University of Antwerp, Antwerp, Belgium. 3. AUDACIS, Antwerp Unit for Data Analysis and Computation in Immunology and Sequencing, University of Antwerp, Antwerp, Belgium; Centre for Health Economics Research & Modeling Infectious Diseases (CHERMID), Vaccine & Infectious Disease Institute (VAXINFECTIO), University of Antwerp, Antwerp, Belgium. 4. AUDACIS, Antwerp Unit for Data Analysis and Computation in Immunology and Sequencing, University of Antwerp, Antwerp, Belgium; Laboratory of Experimental Hematology (LEH), Vaccine & Infectious Disease Institute (VAXINFECTIO), University of Antwerp, Antwerp, Belgium. 5. Department of Laboratory Medicine, Antwerp University Hospital, Edegem, Belgium. 6. AUDACIS, Antwerp Unit for Data Analysis and Computation in Immunology and Sequencing, University of Antwerp, Antwerp, Belgium; Centre for Health Economics Research & Modeling Infectious Diseases (CHERMID), Vaccine & Infectious Disease Institute (VAXINFECTIO), University of Antwerp, Antwerp, Belgium; Interuniversity Institute for Biostatistics and Statistical Bioinformatics, Hasselt University, Diepenbeek, Belgium; Centre for the Evaluation of Vaccination (CEV), Vaccine & Infectious Disease Institute (VAXINFECTIO), University of Antwerp, Antwerp, Belgium. 7. AUDACIS, Antwerp Unit for Data Analysis and Computation in Immunology and Sequencing, University of Antwerp, Antwerp, Belgium; Laboratory of Experimental Hematology (LEH), Vaccine & Infectious Disease Institute (VAXINFECTIO), University of Antwerp, Antwerp, Belgium; Center for Cell Therapy and Regenerative Medicine, Antwerp University Hospital, Edegem, Belgium; Center for Oncological Research Antwerp, University of Antwerp, Antwerp, Belgium. 8. AUDACIS, Antwerp Unit for Data Analysis and Computation in Immunology and Sequencing, University of Antwerp, Antwerp, Belgium; Centre for the Evaluation of Vaccination (CEV), Vaccine & Infectious Disease Institute (VAXINFECTIO), University of Antwerp, Antwerp, Belgium. 9. AUDACIS, Antwerp Unit for Data Analysis and Computation in Immunology and Sequencing, University of Antwerp, Antwerp, Belgium; Centre for Health Economics Research & Modeling Infectious Diseases (CHERMID), Vaccine & Infectious Disease Institute (VAXINFECTIO), University of Antwerp, Antwerp, Belgium; Laboratory of Experimental Hematology (LEH), Vaccine & Infectious Disease Institute (VAXINFECTIO), University of Antwerp, Antwerp, Belgium; Department of Paediatrics, Antwerp University Hospital, Edegem, Belgium. 10. Department of Medical Genetics, University of Antwerp/Antwerp University Hospital, Edegem, Belgium; AUDACIS, Antwerp Unit for Data Analysis and Computation in Immunology and Sequencing, University of Antwerp, Antwerp, Belgium. Electronic address: geert.mortier@uantwerpen.be.
Abstract
INTRODUCTION: As the hepatitis B virus is widely spread and responsible for considerable morbidity and mortality, WHO recommends vaccination from infancy to reduce acute infection and chronic carriers. However, current subunit vaccines are not 100% efficacious and leave 5-10% of recipients unprotected. METHODS: To evaluate immune responses after Engerix-B vaccination, we determined, using mRNA-sequencing, whole blood early gene expression signatures before, at day 3 and day 7 after the first dose and correlated this with the resulting antibody titer after two vaccine doses. RESULTS: Our results indicate that immune related genes are differentially expressed in responders mostly at day 3 and in non-responders mostly at day 7. The most remarkable difference between responders and non-responders were the differentially expressed genes before vaccination. The granulin precursor gene (GRN) was significantly downregulated in responders while upregulated in non-responders at day 0. Furthermore, absolute granulocytes numbers were significantly higher in non-responders at day 0. CONCLUSION: The non-responders already showed an activated state of the immune system before vaccination. Furthermore, after vaccination, they exhibited a delayed and partial immune response in comparison to the responders. Our data may indicate that the baseline and untriggered immune system can influence the response upon hepatitis B vaccination.
INTRODUCTION: As the hepatitis B virus is widely spread and responsible for considerable morbidity and mortality, WHO recommends vaccination from infancy to reduce acute infection and chronic carriers. However, current subunit vaccines are not 100% efficacious and leave 5-10% of recipients unprotected. METHODS: To evaluate immune responses after Engerix-B vaccination, we determined, using mRNA-sequencing, whole blood early gene expression signatures before, at day 3 and day 7 after the first dose and correlated this with the resulting antibody titer after two vaccine doses. RESULTS: Our results indicate that immune related genes are differentially expressed in responders mostly at day 3 and in non-responders mostly at day 7. The most remarkable difference between responders and non-responders were the differentially expressed genes before vaccination. The granulin precursor gene (GRN) was significantly downregulated in responders while upregulated in non-responders at day 0. Furthermore, absolute granulocytes numbers were significantly higher in non-responders at day 0. CONCLUSION: The non-responders already showed an activated state of the immune system before vaccination. Furthermore, after vaccination, they exhibited a delayed and partial immune response in comparison to the responders. Our data may indicate that the baseline and untriggered immune system can influence the response upon hepatitis B vaccination.
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