Individuals who do not produce protective antibodies following hepatitis B vaccination are at risk of infection with the virus. The researchers examined the transcriptome of peripheral blood mononuclear cells (PBMCs) for a study to determine the features of gene expression in non-responders. For a trial, the researchers included 7 seven responders who had previously received three shots and 7 seven non-responders who had previously received 6 six doses of hepatitis B vaccination. Following that, all patients were immunized with a three-dose booster regimen. In non-responders and responders, mRNA expression and Th1/Th2/Th9/Th17/Th22/Treg cytokine and chemokine profiles were examined using microarray analysis and the Luminex test. 

Differentially expressed genes in non-responders’ PBMCs at five time periods, namely pre-vaccination, the 3rd, 7th, and 28th days after the first dose vaccination, and the 7th day after the second dose vaccination revealed a dense network pattern. When compared to responders, nine coding genes (BPI, DEFA1B, DEFA4, CEACAM8, MMP8, FOLR3, LTF, TCN1, and TKTL1) were significantly up-regulated in non-responders at all five time periods, suggesting that these genes were the hallmarks of hepatitis B vaccination non-responsiveness. According to gene ontology analysis, the majority of the DEGs were associated with immunological responses. The 9 genes’ validation results using quantitative real-time polymerase chain reaction were mainly compatible with the microarray results. On the third day after the first dose and the 7th day after the second dose of immunization, IL-27 and CXCL12 concentrations in responders were considerably greater than in non-responders, according to cytokine analyses. Other cytokine and chemokine profiles did not differ significantly between the two groups. 

Finally, the findings demonstrated distinct transcriptome and cytokine alterations in hepatitis B vaccination non-responders following boost immunization.