Adoptive transfer of immunity

TY - JOUR

T1 - Adoptive transfer of immunity

T2 - a new strategy to interfere with severe hepatitis virus reinfection after woodchuck liver transplantation

AU - Dahmen, Uta

AU - Dirsch, Olaf

AU - Li, Jun

AU - Fiedle, Melanie

AU - Lu, Mengj

AU - Rispeter, Kai

AU - Picucci, Martha

AU - Broelsch, Christoph E

AU - Roggendorf, Michael

PY - 2004/4/15

Y1 - 2004/4/15

N2 - BACKGROUND: The effective transfer of humoral immunity to hepatitis B virus was first demonstrated after clinical and experimental bone marrow transplantation. This strategy is now evaluated in the woodchuck transplantation model, in which protection from reinfection can be tested.METHODS: Animals negative for woodchuck hepatitis virus (WHV) (n = 3) were vaccinated using plasmids expressing woodchuck hepatitis virus surface (WHs), woodchuck hepatitis virus core (WHc), and woodchuck interferon-gamma in combination with a protein vaccine (WHs antigen [Ag]) three times before liver donation. Control animals (n= 4) received the liver from non-immunized donors. Chronic WHV carriers served as recipients. The viral load in serum and liver tissue was monitored pretransplant and posttransplant for up to 11 weeks by dot blot, Northern blot, Southern blot, and immunohistochemistry for WHc and WhsAg.RESULTS: Donor vaccination was effective, as indicated by the development of anti-WHc and anti-WHs antibodies. Transplanting the livers of these donors resulted in a reduction of viral load in two of three animals. No viral DNA was detected in repeated serum samples by dot-blot hybridization technique. However, polymerase chain reaction for viral DNA extracted from serum was always positive. WHV replication intermediates and WHV RNA were absent in repeated liver biopsies. Only few hepatocytes stained weakly positive for WHc protein and frequency, and the intensity of WHsAg positive hepatocytes was low. The third animal developed severe reinfection within 3 weeks, similar to the woodchucks in the control group.CONCLUSIONS: Liver transplantation from immunized donors to chronic carriers seems to be a promising strategy to reduce and delay severe reinfection, which may be applicable in clinical liver transplantation.

AB - BACKGROUND: The effective transfer of humoral immunity to hepatitis B virus was first demonstrated after clinical and experimental bone marrow transplantation. This strategy is now evaluated in the woodchuck transplantation model, in which protection from reinfection can be tested.METHODS: Animals negative for woodchuck hepatitis virus (WHV) (n = 3) were vaccinated using plasmids expressing woodchuck hepatitis virus surface (WHs), woodchuck hepatitis virus core (WHc), and woodchuck interferon-gamma in combination with a protein vaccine (WHs antigen [Ag]) three times before liver donation. Control animals (n= 4) received the liver from non-immunized donors. Chronic WHV carriers served as recipients. The viral load in serum and liver tissue was monitored pretransplant and posttransplant for up to 11 weeks by dot blot, Northern blot, Southern blot, and immunohistochemistry for WHc and WhsAg.RESULTS: Donor vaccination was effective, as indicated by the development of anti-WHc and anti-WHs antibodies. Transplanting the livers of these donors resulted in a reduction of viral load in two of three animals. No viral DNA was detected in repeated serum samples by dot-blot hybridization technique. However, polymerase chain reaction for viral DNA extracted from serum was always positive. WHV replication intermediates and WHV RNA were absent in repeated liver biopsies. Only few hepatocytes stained weakly positive for WHc protein and frequency, and the intensity of WHsAg positive hepatocytes was low. The third animal developed severe reinfection within 3 weeks, similar to the woodchucks in the control group.CONCLUSIONS: Liver transplantation from immunized donors to chronic carriers seems to be a promising strategy to reduce and delay severe reinfection, which may be applicable in clinical liver transplantation.

KW - Animals

KW - DNA, Viral

KW - Hepatitis B

KW - Hepatitis B Antibodies

KW - Hepatitis B Virus, Woodchuck

KW - Humans

KW - Immunotherapy, Adoptive

KW - Liver

KW - Liver Transplantation

KW - Marmota

KW - RNA, Viral

KW - Recurrence

KW - Vaccination

KW - Viral Proteins

KW - Journal Article

KW - Research Support, Non-U.S. Gov't

M3 - SCORING: Journal article

C2 - 15087755

VL - 77

SP - 965

EP - 972

JO - TRANSPLANTATION

JF - TRANSPLANTATION

SN - 0041-1337

IS - 7

ER -