Transcriptome profiling in blood before and after hepatitis B vaccination shows significant differences in gene expression between responders and non-responders

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.

Keywords: Differential gene expression; Engerix-B vaccine; Hepatitis B; Immune response.