Effects of adjuvants (granulocyte-macrophage colony-stimulating factor, levamisole, adjuvant system 04, adjuvant system 02B) on enhancing immune response to hepatitis B vaccine: a systematic review and meta-analysis

Background and objective: Hepatitis B virus (HBV) is known as one of the prevalent infectious diseases considered a public health problem in numerous countries. At present, the only safe prevention strategy is vaccination, but it cannot provide complete immunity. We aimed to evaluate the effect of granulocyte-macrophage colony-stimulating factor (GM-CSF), levamisole, adjuvant system 04 (AS04), and adjuvant system 02B (AS02B) as adjuvants in HBV vaccination. Methods: The databases of ScienceDirect, MEDLIB-ED, PubMed, and Embase were systematically searched using valid keywords. Controlled clinical trial studies, which evaluated the response rate of the population to the HBV vaccine alone (control group) compared with the HBV vaccine combined with adjuvants (study group) were included in this review. The data were analyzed through a random-effects meta-analysis model using R programming language and Stata (version 11.2). Results: A total of 36 article including 4805 participants were included in this review. The findings revealed that the response rate to HBV vaccination for levamisole in the study group was 46.1% (95% confidence interval (CI) [38–51]), and that was 43.8% (95% CI [36–51]) in the control group. These values were also 56.8% (95% CI [53–60]) and 43.3% (95% CI [40–46.7]) for GM-CSF in the study group and the control group, respectively. Considering AS04, the response rate in the study group was 50.8% (95% CI [40–61]), and that was 45.8% (95% CI [37–54]) in the control group. Moreover, these values were 86.3% (95% CI [75–95]) and 47.6% (95% CI [31–63]) for AS02B in the study group and the control group, respectively. Conclusion: The results of this meta-analysis demonstrated the significant benefit of using GM-CSF, levamisole, AS04, and AS02B as adjuvants to boost the immunogenicity of the HBV vaccine.