TY - JOUR
T1 - Therapeutic vaccination of woodchucks against chronic woodchuck hepatitis virus infection
AU - Hervás-Stubbs, Sandra
AU - Lasarte, Juan José
AU - Sarobe, Pablo
AU - Prieto, Jesús
AU - Cullen, John
AU - Roggendorf, Michael
AU - Borrás-Cuesta, Francisco
N1 - Funding Information:
We are grateful to Gobierno de Navarra, Direcci6n General de Investigaci6n Cientitica y T6cnica (PB93-1227), Fundaci6n Ech6bano, PIUNA, and Deutsche Forchungs Gemeinschaft (Gesch Z: RO 687/2-2) for financial support. We also thank I. Monreal for the analysis of y-GTP and bilirubin, J. Longo and M. D. Barettino for carrying out the ultrasound explorations and T. Tolle for the setup of the experimental animal model.
PY - 1997/10
Y1 - 1997/10
N2 - Background/Aims: Therapeutic vaccination is a new approach to treat patients with chronic hepatitis B virus infection. We have used the woodchuck model to examine the efficacy and safety of this approach. Methods: Seven woodchucks chronically infected with woodchuck hepatitis virus were immunized with surface antigen from this virus, purified from plasma, in conjunction with a peptide named FIS (encompassing amino acids 106-118: FISEAIIHVLHSR from sperm whale myoglobin), which is recognized by T helper lymphocytes. As controls, two woodchucks chronically infected with woodchuck hepatitis virus were immunized: one with FIS only and the other with surface antigen only. Results: Co-immunization with surface antigen and FIS, but not with FIS or surface antigen alone, induced anti-surface antibodies in 7/7 immunized woodchucks. In the two woodchucks in which the highest titer of anti-surface antibody was elicited, severe liver damage was observed: one died of fulminant hepatitis and the other became seriously ill with hepatic injury and had to be sacrificed. Conclusions: Co-immunization of chronically infected woodchucks with surface antigen and a peptide recognized by T helper cells produces a good anti-surface antibody response. However, this strategy needs to be optimized before its implementation in humans. Although our experiments are not strictly comparable to vaccination of chronically hepatitis B virus-infected patients with recombinant or plasma-derived vaccines, we believe that precautions should be taken to avoid the risk of severe liver injury when immunizing hepatitis B virus carriers.
AB - Background/Aims: Therapeutic vaccination is a new approach to treat patients with chronic hepatitis B virus infection. We have used the woodchuck model to examine the efficacy and safety of this approach. Methods: Seven woodchucks chronically infected with woodchuck hepatitis virus were immunized with surface antigen from this virus, purified from plasma, in conjunction with a peptide named FIS (encompassing amino acids 106-118: FISEAIIHVLHSR from sperm whale myoglobin), which is recognized by T helper lymphocytes. As controls, two woodchucks chronically infected with woodchuck hepatitis virus were immunized: one with FIS only and the other with surface antigen only. Results: Co-immunization with surface antigen and FIS, but not with FIS or surface antigen alone, induced anti-surface antibodies in 7/7 immunized woodchucks. In the two woodchucks in which the highest titer of anti-surface antibody was elicited, severe liver damage was observed: one died of fulminant hepatitis and the other became seriously ill with hepatic injury and had to be sacrificed. Conclusions: Co-immunization of chronically infected woodchucks with surface antigen and a peptide recognized by T helper cells produces a good anti-surface antibody response. However, this strategy needs to be optimized before its implementation in humans. Although our experiments are not strictly comparable to vaccination of chronically hepatitis B virus-infected patients with recombinant or plasma-derived vaccines, we believe that precautions should be taken to avoid the risk of severe liver injury when immunizing hepatitis B virus carriers.
KW - Antibodies
KW - Hepatitis
KW - Immune therapy
KW - Peptides
KW - T-cell help
KW - Vaccination
KW - Woodchuck
KW - Woodchuck hepatitis virus (WHV)
KW - Woodchuck hepatitis virus surface antigen (WHsAg)
UR - http://www.scopus.com/inward/record.url?scp=0343471379&partnerID=8YFLogxK
U2 - 10.1016/S0168-8278(97)80090-6
DO - 10.1016/S0168-8278(97)80090-6
M3 - Article
C2 - 9365049
AN - SCOPUS:0343471379
SN - 0168-8278
VL - 27
SP - 726
EP - 737
JO - Journal of Hepatology
JF - Journal of Hepatology
IS - 4
ER -