Administration of a human monoclonal antibody (TUVIRUMAB) to chronic hepatitis B patients pre-treated with lamivudine: Monitoring of serum TUVIRUMAB in immune complexes

A human monoclonal anti-hepatitis B antibody preparation(TUV1RUMAB) was adm inistered 6 times over a 2-week period in a dose-escalating scheme to chron ic hepatitis B patients pre-treated with lamivudine. The capacity of the TU VIRUMAB antibody to "neutralize" hepatitis B surface antigen in the circula tion was investigated by means of experimental enzyme-immunoassays. Monoclo nal antibody conjugates enabled the detection of HBsAg, TUVIRUMAB, and HBsA g/TUVIRUMAB complexes. The results showed that (1) TUVIRUMAB was able parti ally to "neutralize" in vitro and in vivo, (2) HBsAg/TUVIRUMAB complexes ca n be traced by assays that capture the complex at either its HBsAg or its T UVIRUMAB component, (3) the final concentration of TUVIRUMAB at the end of therapy varied greatly but seemed to be related to HBsAg production at the start of therapy, (4) for at least 14 days after discontinuation of therapy , a minimal HBsAg level could be maintained in the presence of a declining TUVIRUMAB titer in patients with less than 3 mug/ml HBsAg before the start of therapy, (5) three months after therapy, all HBsAg levels had returned t o pretreatment levels and TUVIRUMAB had disappeared. J. Med. Virol. 64:427- 434, 2001. (C) 2001 Wiley-Liss, Inc.