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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

Experimental schedule of the pilot-clinical study. Lamivudine treatment for 8 weeks had been preceded before the first HB-100 injection at T1 except for three subjects; V#118 at week 4, and V#105 and V#106 at week 12. The vaccinees were intramuscularly administrated 12 times with 8 mg of HB-100 every 4 weeks as indicated by the arrows in combination with 100 mg of LAM treatment daily for 52 weeks (gray rectangles) and another 52 weeks were followed (white rectangles). Plasma samples were obtained every 4 weeks (black circles) and the level of cytokines was evaluated by ELISA assay.
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Figure 1: Experimental schedule of the pilot-clinical study. Lamivudine treatment for 8 weeks had been preceded before the first HB-100 injection at T1 except for three subjects; V#118 at week 4, and V#105 and V#106 at week 12. The vaccinees were intramuscularly administrated 12 times with 8 mg of HB-100 every 4 weeks as indicated by the arrows in combination with 100 mg of LAM treatment daily for 52 weeks (gray rectangles) and another 52 weeks were followed (white rectangles). Plasma samples were obtained every 4 weeks (black circles) and the level of cytokines was evaluated by ELISA assay.

Mentions: We assessed plasma samples from 12 CHB carriers treated with combined therapy of DNA vaccine plus lamivudine as previously reported (3). Briefly, represented in Fig. 1, 12 Caucasian CHB carriers were enrolled from Ukraine and Lithuania and injected 12 times with 8 mg of HB-100 expressing HBV S, pre S1/S2, core, polymerase, X protein and human IL-12 mutant (hIL-12N222L) intramuscularly at four-week interval in combination with 100 mg of lamivudine (Epivir-HBV, GlaxoSmithKline) daily for 52 weeks. Every 4 week, plasma samples were prepared and delivered to a central laboratory at Pohang University of Science and Technology in Korea using a portable liquid nitrogen tank and subsequently used for ELISA assay. The present study was approved by the Pharmacological Center of the Ministry of Health of Ukraine, by the Commission of Non-clinical and Clinical Trials of the State Medicines Control Agency of the Ministry of Health of Lithuania.


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)

Experimental schedule of the pilot-clinical study. Lamivudine treatment for 8 weeks had been preceded before the first HB-100 injection at T1 except for three subjects; V#118 at week 4, and V#105 and V#106 at week 12. The vaccinees were intramuscularly administrated 12 times with 8 mg of HB-100 every 4 weeks as indicated by the arrows in combination with 100 mg of LAM treatment daily for 52 weeks (gray rectangles) and another 52 weeks were followed (white rectangles). Plasma samples were obtained every 4 weeks (black circles) and the level of cytokines was evaluated by ELISA assay.
© Copyright Policy - open-access
Related In: Results  -  Collection

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

Figure 1: Experimental schedule of the pilot-clinical study. Lamivudine treatment for 8 weeks had been preceded before the first HB-100 injection at T1 except for three subjects; V#118 at week 4, and V#105 and V#106 at week 12. The vaccinees were intramuscularly administrated 12 times with 8 mg of HB-100 every 4 weeks as indicated by the arrows in combination with 100 mg of LAM treatment daily for 52 weeks (gray rectangles) and another 52 weeks were followed (white rectangles). Plasma samples were obtained every 4 weeks (black circles) and the level of cytokines was evaluated by ELISA assay.
Mentions: We assessed plasma samples from 12 CHB carriers treated with combined therapy of DNA vaccine plus lamivudine as previously reported (3). Briefly, represented in Fig. 1, 12 Caucasian CHB carriers were enrolled from Ukraine and Lithuania and injected 12 times with 8 mg of HB-100 expressing HBV S, pre S1/S2, core, polymerase, X protein and human IL-12 mutant (hIL-12N222L) intramuscularly at four-week interval in combination with 100 mg of lamivudine (Epivir-HBV, GlaxoSmithKline) daily for 52 weeks. Every 4 week, plasma samples were prepared and delivered to a central laboratory at Pohang University of Science and Technology in Korea using a portable liquid nitrogen tank and subsequently used for ELISA assay. The present study was approved by the Pharmacological Center of the Ministry of Health of Ukraine, by the Commission of Non-clinical and Clinical Trials of the State Medicines Control Agency of the Ministry of Health of Lithuania.

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