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
The risk factors associated with the progression of IgA nephropathy (IgAN), the most common form of glomerulonephritis, are unclear. It has been suggested that CD14 signalling in response to various microbes affects the natural history of chronic inflammatory conditions. It has been hypothesised that variants in the promoter region of the CD14 gene might alter the expression of CD14, and this in turn could influence the progressive nature of IgAN. PCR-RFLP was used to determine the polymorphism at the −159 site (T to C). The distribution of the CD14/−159 polymorphism was no different in patients with IgAN (n=216) compared to 171 healthy controls. After follow up for 86 months, it was found that an excess of the C genotype occurred in patients with progressive disease (p=0.03) and the risk of disease progression increased as the number of C alleles increased (p for trend = 0.002). The hazard ratio for progression in the patients with the CC genotype was 3.2 (p=0.025) compared with the patients possessing the TT genotype. After LPS stimulation, sCD14 was released more abundantly from the PBMCs of the TT subjects than from that of the CC subjects (p=0.006), even though mCD14 expression level was no different. In addition, the TT subjects released less IL-6 than the CC subjects after stimulation (p=0.0003). These results suggest that the CD14/−159 polymorphism is an important marker for the progression of IgAN and may modulate the level of the inflammatory responses.
A novel cytokine interleukin (IL)-23 bears a structural and functional resemblance to IL-12. A recombinant adenovirus expressing IL-23N220L (recombinant replication-defective adenovirus (rAd)/IL-23N220L) that selectively secrets IL-23 was constructed and compared with rAd/IL-12N220L in terms of immunological and antitumor effects. In a prophylactic setting, vaccination with rAd/ ovalbumin (OVA) and rAd/IL-23N220L enhanced OVA-specific CD8 þ T-cell responses that were closely associated with complete protection against the subsequent challenge of OVA-expressing E.G7 thymoma. However, in a therapeutic setting, the intratumoral injection of rAd/IL-23N220L showed only marginal antitumor activity against several established tumors such as E.G7, CT26 and B16F10. Interestingly, whereas IL-23 still induced tumor-specific CD8 þ T-cell responses, it could not activate natural killer (NK) cells in vitro and in vivo. In addition, the adoptive transfer of activated NK cells partially restored the therapeutic antitumor effect of IL-23, indicating that NK cells are one of the crucial factors responsible for the regression of established tumors. Taken together, we demonstrated that adenovirus-mediated gene transfer of IL-23 induces a potent prophylactic, but not a therapeutic, antitumor effect.
Due to its superb seeing conditions, the Antarctica plateau is widely considered to be an excellent astronomical site. The long periods of uninterrupted darkness at polar sites such as Dome A provide a possibility of continuous observation for more than three months, which is quite suitable for time-domain astronomy. Since 2008, several wide-field optical photometric telescopes, including Chinese Small Telescope ARray (CSTAR), two of the Three Antarctic Survey Telescopes (AST3), have been deployed on Dome A. Science with these telescopes covers variable stars, supernovas, exoplanets, etc. For the remoteness of the Antarctic plateau, these telescopes are designed to observe autonomously and operate remotely via satellite communication. As for future plan, Kunlun Dark Universe Survey Telescope (KDUST), a 2.5-meter optic/infrared telescope, is being proposed as one of the two major facilities of Chinese Antarctic Observatory.
scite is a Brooklyn-based organization that helps researchers better discover and understand research articles through Smart Citations–citations that display the context of the citation and describe whether the article provides supporting or contrasting evidence. scite is used by students and researchers from around the world and is funded in part by the National Science Foundation and the National Institute on Drug Abuse of the National Institutes of Health.
customersupport@researchsolutions.com
10624 S. Eastern Ave., Ste. A-614
Henderson, NV 89052, USA
This site is protected by reCAPTCHA and the Google Privacy Policy and Terms of Service apply.
Copyright © 2024 scite LLC. All rights reserved.
Made with 💙 for researchers
Part of the Research Solutions Family.