Advances in immunomodulating therapy of HBV infection
Found an interesting read from 2005.. http://www.medsci.org/v02p0024.htm
some of the information they knew as far back as 1990's - and all these treatment strategies are so slowly being moved forward on with. Cures are there folks, and better treatments..
ADOPTIVE TRANSFER OF IMMUNITY.
In both animal and human studies, transfer of HBV immune memory from a immune donor through bone marrow transplantation (BMT) or peripheral blood lymphocytes (PBLs) has enabled seroconversion to Hepatitis B surface antibody in HBV naïve recipients [13-16]. Furthermore, clearance of HBsAg has been observed in individual patients with chronic hepatitis B after transplantation of bone marrow from HBV immune donors [17-19]. By studying the largest series of patients, who cleared HBsAg following the engraftment of an HLA-identical bone marrow from a donor with past exposure to HBV, we found that resolution of chronic HBV infection is associated with a transfer of CD4+ T lymphocyte reactivity to HBcAg, rather than to HBV envelope proteins . We have demonstrated that the CD4+ T cells are of donor origin and activation of the memory subset, CD45-RO+ T cells, occurs during the hepatitis flare, which precedes the seroconversion to anti-HBs. These results explain our earlier clinical observation that HBsAg clearance occurs only after adoptive transfer of naturally acquired immunity to HBV (anti-HBs and anti-HBc positive donors) and not in patients who received marrow with a vaccine-induced immunity (anti-HBs alone) . The practical implication of the present findings of successful HBsAg clearance following adoptive transfer of immunity to HBcAg, is that therapeutic immunization of patients with chronic HBV infection should include the HBV nucleocapsid protein (or the core gene for DNA immunization) and aim to induce both HBcAg-specific CD4+ and CD8+ T cell responses.
However, although adoptive transfer is an interesting alternative for the treatment of chronic HBV infection, it is associated with certain risks. The risks of adoptive transfer are those associated with BMT and the absence of immune control that may result in infections, veno-occlusive disease and graft-versus-host disease. Fulminant hepatitis resulting in hepatic failure has also been reported following adoptive transfer of immunity to HBV . Thus, although adoptive transfer of immunity to HBV is a possible approach, it is restricted to the BMT setting and is limited by its potential serious complications.
Adoptive transfer of immunity to HBV has also been reported in patients after liver transplantation . Spontaneous production of anti-HBs is observed in 21 of 50 HBsAg+ patients (42%) receiving lamivudine monoprophylaxis after liver transplantation. Seroconversion to anti-HBs can be detected in a median of eight days. In those that developed anti-HBs seroconversion, a more rapid clearance of HBsAg is also observed and the predictor of anti-HBs production is an HBV-immune donor, suggesting the possibility of adoptive immunity transfer through a liver graft. The same could be observed in rats after kidney transplantation .
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