Therapeutic vaccination of woodchucks against chronic woodchuck hepatitis virus infection

JOURNAL OF HEPATOLOGY

卷:27

Article

HervasStubbs, S ; Lasarte, JJ ; Sarobe, P ; Prieto, J ; Cullen, J ; Roggendorf, M ; BorrasCuesta, F

关键词: antibodies;    hepatitis;    immune therapy;    peptides;    T-cell help;    vaccination;    woodchuck;    woodchuck hepatitis virus (WHV);    woodchuck hepatitis virus surface antigen (WHsAg);   

DOI  :  10.1016/S0168-8278(97)80090-6

来源: Elsevier

【 摘 要 】

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.

【 授权许可】

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