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

Abstract

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.

Public broadly neutralizing antibodies against hepatitis B virus in individuals with elite serologic activity

“…The near identity of clones of HBV bNAbs in unrelated elite individuals is akin to reports for elite responders to HIV-1 (Scheid et al, 2011; West et al, 2012), influenza (Laursen and Wilson, 2013; Pappas et al, 2014; Wrammert et al, 2011), Zika (Robbiani et al, 2017), and malaria (Tan et al, 2018). However, none of the elite anti-HBs bNAbs shares both IgH and IgL with previously reported HBV neutralizing antibodies, the best of which have been tested in the clinic but are less potent than some of the bNAbs reported here (libivirumab IC 50 : 35 ng/ml, tuvirumab IC 50 : ~100 ng/ml) (Galun et al, 2002; Heijtink et al, 2001; van Nunen et al, 2001).…”

Antepartum immunoprophylaxis of three doses of hepatitis B immunoglobulin is not effective: a single‐centre randomized study

“…Moreover, its half‐life is short. Therefore, if HBV is actively replicating, which is the case in the HBeAg‐positive patients, the neutralization efficacy of HBIg should be limited and transitory [20,21].…”

“…Complete neutralization of HBsAg by HBIg in vitro was possible, and 50% inhibition with HBsAg levels of 68 and 120 ng/mL was achieved with concentrations between 100 and 250 IU/L HBIg [20]. Yet, in vivo neutralization of HBsAg by HBIg was achieved only in patients with low HBsAg levels [20,21]. No information on how to determine the dose and the frequency of this regimen is available [10–19].…”

“…It has been demonstrated that perinatal infections of babies born to HBeAg‐negative mothers could be satisfactorily prevented by postnatal hepatitis B immunization [3–6]. In previous studies on nonpregnant CHB patients, neutralization of hepatitis B surface antigen (HBsAg) by HBIg was achieved only in patients with low HBsAg levels [20,21]. Therefore, antenatal treatment of HBIg should emphasize on the HBeAg‐positive women; however, it is questionable that this regimen can significantly reduce the viraemia levels of the HBeAg‐positive women.…”

Human monoclonal single-chain antibodies specific to dengue virus envelope protein

“…Various types of antibodies against viral and bacterial infection were tested in vitro , in animal models and in clinical trials (Heijtink et al . ; Domanski et al . ; Taylor et al .…”