Therapeutic vaccination of woodchucks against chronic woodchuck hepatitis virus infection
Keywords: 
Antibodies
Hepatitis
Immune therapy
Peptides
T-cell help
Vaccination
Woodchuck
Woodchuck hepatitis virus (WHV)
Woodchuck hepatitis virus surface antigen (WHsAg)
Issue Date: 
1997
Publisher: 
Elsevier
ISSN: 
1600-0641
Citation: 
Hervas-Stubbs S, Lasarte JJ, Sarobe P, Prieto J, Cullen J, Roggendorf M, et al. Therapeutic vaccination of woodchucks against chronic woodchuck hepatitis virus infection. J Hepatol 1997 Oct;27(4):726-737.
Abstract
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.

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