Despite recent advances in the chemotherapy of chronic hepatitis B (CHB), an effective viral suppression after cessation of therapy has not yet been achieved. To investigate whether hepatitis B virus (HBV)-specific T-cell responses are inducible and can contribute to the viral suppression after cessation of the therapy, we conducted a proof-of-concept study with a DNA vaccine comprising of most HBV genes plus genetically engineered interleukin-12 DNA (IL-12N222L) in 12 CHB carriers being treated with lamivudine (LAM). When the ex vivo and/or cultured IFN-g enzyme-linked immunospot (ELISPOT) assay was performed, the detectable HBV-specific IFN-g secreting T-cell responses were observed at the end of treatment and during a follow-up. These type 1T-cell responses, particularly CD4 + memory T-cell responses could be maintained for at least 40 weeks after the therapy and correlated with virological responses, but not with alanine aminotransferase elevation. Moreover, DNA vaccination under LAM treatment appeared to be well-tolerated and showed 50% of virological response rate in CHB carriers. Thus, a combination therapy of the DNA vaccine with chemotherapy may be one of new immunotherapeutic methods for the cure of CHB. Gene Therapy ( Patients with chronic HBV infection who showed remission also develop vigorous CTL and strong type 1T helper (Th1) immune responses that are comparable to those in patients who have a selflimited disease. 4 In contrast, the CTL and Th1 responses are undetectable or relatively weak in patients with chronic HBV infection. 3,5 Lamivudine (LAM) and adefovir dipivoxil as nucleoside analogues can suppress HBV replication effectively during treatment period, 6,7 but their use is limited by the high risk of viral relapse upon discontinuation even after long-term treatment.2 A restoration of HBV-specific CD4 + and CD8 + T-cell responses by LAM monotherapy was previously observed, but these T-cell responses were not only transient during treatment, but were also undetectable or very weak at the end of 1-year treatment. 8,9 It was recently reported that the inverse correlation between the number of antigen-specific interferon (IFN)-g producing CD4 + T cells and serum HBV DNA was observed during the treatment of LAM with recombinant interleukin-12 (IL-12) protein, but not detectable after the treatment.
10Therefore, further studies are needed to elucidate the relationship between T-cell responses and the suppression of viral relapse after stopping the therapy.DNA vaccine has the advantage of inducing both humoral and cellular immune responses, especially Th1 and CTL responses. HBV DNA vaccine was shown to induce strong T-cell responses, leading to the suppression of viral replication in HBV transgenic mice.11 In contrast, DNA immunization induced very weak T-cell
Infrared reflection absorption spectroscopy (IRAS) has been used to study CO-NO and CO-O(2) interactions on Cu(100) between 25 and 200 K. A strong repulsive interaction between CO and NO on Cu(100) at 25 K causes tilting of the CO molecules away from the surface normal and a blue-shift of the CO vibrational frequency. Upon warming and decomposition of the NO, the CO molecules return to a bonding position normal to the surface plane. The vibrational frequency of CO blue-shifts from 2087 to 2136 cm(-1) upon coadsorption with N and O atoms formed from NO decomposition. On the other hand, the interaction of CO with O(2) at 27 K on Cu(100) in the submonolayer regime induces a red-shift of the CO vibrational frequency. Atomic oxygen, formed on Cu(100) by dissociation of O(2) at 95 K, induces a blue-shift of the vibrational frequency of coadsorbed CO to 2116 cm(-1). The CO vibrational frequency shifts to 2091 cm(-1) when the surface is annealed to 140 K, implying a change in the adsorption geometry of the oxygen atoms on Cu(100).
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