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 (TUVIRUMAB) was administered 6 times over a 2-week period in a dose-escalating scheme to chronic hepatitis B patients pre-treated with lamivudine. The capacity of the TUVIRUMAB antibody to "neutralize" hepatitis B surface antigen in the circulation was investigated by means of experimental enzyme-immunoassays. Monoclonal antibody conjugates enabled the detection of HBsAg, TUVIRUMAB, and HBsAg/TUVIRUMAB complexes. The results showed that (1) TUVIRUMAB was able partially to "neutralize" in vitro and in vivo, (2) HBsAg/TUVIRUMAB complexes can be traced by assays that capture the complex at either its HBsAg or its TUVIRUMAB 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 microg/ml HBsAg before the start of therapy, (5) three months after therapy, all HBsAg levels had returned to pre-treatment levels and TUVIRUMAB had disappeared.
Heijtink
R A
RA
Department of Virology, Erasmus University Rotterdam, Rotterdam, The Netherlands. heijtink@viro.fgg.eur.nl
van Nunen
A B
AB
van Bergen
P
P
Ostberg
L
L
Osterhaus
A D
AD
de Man
R A
RA
D000911:Antibodies, Monoclonal / Q000097:blood / Q000627:therapeutic use*; D000936:Antigen-Antibody Complex / Q000097:blood*; D015331:Cohort Studies; D004305:Dose-Response Relationship, Drug; D006510:Hepatitis B Antibodies / Q000032:analysis / Q000627:therapeutic use*; D006514:Hepatitis B Surface Antigens / Q000032:analysis / Q000276:immunology; D019694:Hepatitis B, Chronic / Q000097:blood / Q000628:therapy* / Q000821:virology; D006801:Humans; D007275:Injections, Intravenous; D019259:Lamivudine / Q000627:therapeutic use*; D009500:Neutralization Tests; D018894:Reverse Transcriptase Inhibitors / Q000627:therapeutic use*
D000911:Antibodies, Monoclonal; D000936:Antigen-Antibody Complex; D006510:Hepatitis B Antibodies; D006514:Hepatitis B Surface Antigens; D018894:Reverse Transcriptase Inhibitors; D019259:Lamivudine