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Increase of Plasma IL-12/p40 Ratio Induced by the Combined Therapy of DNA Vaccine and Lamivudine Correlates with Sustained Viremia Control in CHB Carriers.

Im SJ, Yang SH, Yoon SK, Sung YC - Immune Netw (2009)

Bottom Line: Twelve CHB carriers were intramuscularly immunized 12 times at a 4-week interval with 8 mg of HBV DNA vaccine during the standard lamivudine treatment (100 mg/daily/1 year).Six out of 12 CHB carriers revisited the clinic, and their HBV DNA levels were examined.In addition, there was no significant temporal correlation between the peak IL-12/p40 ratio and the elevation of serum alanine aminotransferase (ALT) in this study, contrast to IFN-alpha therapy which induced peak IL-12 level following ALT flares.

View Article: PubMed Central - PubMed

Affiliation: Division of Molecular and Life Sciences, Pohang University of Science & Technology, Pohang, Korea.

ABSTRACT

Background: We previously reported that IFN-gamma producing T cell responses induced by the combined therapy of DNA vaccine and lamivudine for one year are important for the induction of sustained virological response (SVR). However, IFN-gamma production is not sufficient to predict sustained viremia control in chronic hepatitis B (CHB) carriers treated.

Methods: Twelve CHB carriers were intramuscularly immunized 12 times at a 4-week interval with 8 mg of HBV DNA vaccine during the standard lamivudine treatment (100 mg/daily/1 year). The level of cytokines during and after the combined therapy in plasma of all 12 CHB carriers treated was determined by each ELISA kit. Six out of 12 CHB carriers revisited the clinic, and their HBV DNA levels were examined.

Results: The combined therapy increased plasma IL-12 and IL-12/p40 ratio during the treatment (baseline vs. peak level: 41.8+/-8.3 vs. 163.1+/-29.2 pg/ml; p<0.01 and 0.96+/-0.25 vs. 3.58+/-0.86; p<0.01, espectively), and the peak level of plasma IL-12 and IL-12/p40 ratio was evoked at 6 to 10 months during the combined therapy. In particular, CHB carriers with SVR had two and three-fold higher level of the peak plasma IL-12 and plasma IL-12/p40 ratio than non-virological responders (NVRs), respectively (218.0+/-41.4 vs. 108.1+/-28.6 pg/ml; p=0.09 and 5.35+/-1.38 vs. 1.80+/-0.29; p<0.05, respectively), while p40 level was consistent during the combined therapy. In addition, there was no significant temporal correlation between the peak IL-12/p40 ratio and the elevation of serum alanine aminotransferase (ALT) in this study, contrast to IFN-alpha therapy which induced peak IL-12 level following ALT flares.

Conclusion: Our results indicate that the combined therapy induces the increase of plasma IL-12 and IL-12/p40 ratio, which are associated with long-term SVR in CHB carriers.

No MeSH data available.


Related in: MedlinePlus

The longitudinal analysis of serum viral loads for up to 3 years in CHB carriers treated with combined therapy. Three VRs (V#103, V#106 and V#113; closed circles) and 3 NVRs (V#105, V#107 and #114; open circles) out of 12 subjects revisited the clinic 3 years after the stopping the combined therapy. Data were represented by the average serum viral loads according to the time point. (mean±SEM).
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Figure 5: The longitudinal analysis of serum viral loads for up to 3 years in CHB carriers treated with combined therapy. Three VRs (V#103, V#106 and V#113; closed circles) and 3 NVRs (V#105, V#107 and #114; open circles) out of 12 subjects revisited the clinic 3 years after the stopping the combined therapy. Data were represented by the average serum viral loads according to the time point. (mean±SEM).

Mentions: Previously, we demonstrated that there were 6 VRs and 6 NVRs, as determined by viral loads at the end of a 1-year follow-up. Among them, six subjects (V#103, V#106 and V#113; VRs and V#105, V#107 and V#114; NVRs) have revisited the clinic 3 years after the cessation of combined therapy. When their serum viral loads were determined to address long-term efficacy of combined therapy, two (V#103, V#106) out of 3 VRs still showed undetectable serum viremia, and one subject (V#113) had a very low level of serum viral load (3,200 copies/ml), reflecting the maintained viremia control for up to 3 years in VRs after the combined therapy (Fig 5). Interestingly, it is likely that all 3 VRs showed strong HBV antigen-specific IFN-γ responses or higher IL-12/p40 ratio (Table I), suggesting that they might be involved in controlled viremia in vaccinees. As expected, one subject (V#106) still maintained HBsAg seroconversion (data not shown). In contrast, all 3 NVRs had high viral loads 3 years after the cessation of combined therapy, even though two of them (V#105 and V#107) had received IFN-α therapy for 6 months after the follow-up period, and their serum viral loads reached more than 200,000 and 162,000,000 copies/ml, respectively.


Increase of Plasma IL-12/p40 Ratio Induced by the Combined Therapy of DNA Vaccine and Lamivudine Correlates with Sustained Viremia Control in CHB Carriers.

Im SJ, Yang SH, Yoon SK, Sung YC - Immune Netw (2009)

The longitudinal analysis of serum viral loads for up to 3 years in CHB carriers treated with combined therapy. Three VRs (V#103, V#106 and V#113; closed circles) and 3 NVRs (V#105, V#107 and #114; open circles) out of 12 subjects revisited the clinic 3 years after the stopping the combined therapy. Data were represented by the average serum viral loads according to the time point. (mean±SEM).
© Copyright Policy - open-access
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC2803296&req=5

Figure 5: The longitudinal analysis of serum viral loads for up to 3 years in CHB carriers treated with combined therapy. Three VRs (V#103, V#106 and V#113; closed circles) and 3 NVRs (V#105, V#107 and #114; open circles) out of 12 subjects revisited the clinic 3 years after the stopping the combined therapy. Data were represented by the average serum viral loads according to the time point. (mean±SEM).
Mentions: Previously, we demonstrated that there were 6 VRs and 6 NVRs, as determined by viral loads at the end of a 1-year follow-up. Among them, six subjects (V#103, V#106 and V#113; VRs and V#105, V#107 and V#114; NVRs) have revisited the clinic 3 years after the cessation of combined therapy. When their serum viral loads were determined to address long-term efficacy of combined therapy, two (V#103, V#106) out of 3 VRs still showed undetectable serum viremia, and one subject (V#113) had a very low level of serum viral load (3,200 copies/ml), reflecting the maintained viremia control for up to 3 years in VRs after the combined therapy (Fig 5). Interestingly, it is likely that all 3 VRs showed strong HBV antigen-specific IFN-γ responses or higher IL-12/p40 ratio (Table I), suggesting that they might be involved in controlled viremia in vaccinees. As expected, one subject (V#106) still maintained HBsAg seroconversion (data not shown). In contrast, all 3 NVRs had high viral loads 3 years after the cessation of combined therapy, even though two of them (V#105 and V#107) had received IFN-α therapy for 6 months after the follow-up period, and their serum viral loads reached more than 200,000 and 162,000,000 copies/ml, respectively.

Bottom Line: Twelve CHB carriers were intramuscularly immunized 12 times at a 4-week interval with 8 mg of HBV DNA vaccine during the standard lamivudine treatment (100 mg/daily/1 year).Six out of 12 CHB carriers revisited the clinic, and their HBV DNA levels were examined.In addition, there was no significant temporal correlation between the peak IL-12/p40 ratio and the elevation of serum alanine aminotransferase (ALT) in this study, contrast to IFN-alpha therapy which induced peak IL-12 level following ALT flares.

View Article: PubMed Central - PubMed

Affiliation: Division of Molecular and Life Sciences, Pohang University of Science & Technology, Pohang, Korea.

ABSTRACT

Background: We previously reported that IFN-gamma producing T cell responses induced by the combined therapy of DNA vaccine and lamivudine for one year are important for the induction of sustained virological response (SVR). However, IFN-gamma production is not sufficient to predict sustained viremia control in chronic hepatitis B (CHB) carriers treated.

Methods: Twelve CHB carriers were intramuscularly immunized 12 times at a 4-week interval with 8 mg of HBV DNA vaccine during the standard lamivudine treatment (100 mg/daily/1 year). The level of cytokines during and after the combined therapy in plasma of all 12 CHB carriers treated was determined by each ELISA kit. Six out of 12 CHB carriers revisited the clinic, and their HBV DNA levels were examined.

Results: The combined therapy increased plasma IL-12 and IL-12/p40 ratio during the treatment (baseline vs. peak level: 41.8+/-8.3 vs. 163.1+/-29.2 pg/ml; p<0.01 and 0.96+/-0.25 vs. 3.58+/-0.86; p<0.01, espectively), and the peak level of plasma IL-12 and IL-12/p40 ratio was evoked at 6 to 10 months during the combined therapy. In particular, CHB carriers with SVR had two and three-fold higher level of the peak plasma IL-12 and plasma IL-12/p40 ratio than non-virological responders (NVRs), respectively (218.0+/-41.4 vs. 108.1+/-28.6 pg/ml; p=0.09 and 5.35+/-1.38 vs. 1.80+/-0.29; p<0.05, respectively), while p40 level was consistent during the combined therapy. In addition, there was no significant temporal correlation between the peak IL-12/p40 ratio and the elevation of serum alanine aminotransferase (ALT) in this study, contrast to IFN-alpha therapy which induced peak IL-12 level following ALT flares.

Conclusion: Our results indicate that the combined therapy induces the increase of plasma IL-12 and IL-12/p40 ratio, which are associated with long-term SVR in CHB carriers.

No MeSH data available.


Related in: MedlinePlus