A 35-year-old female hepatitis B virus carrier chimpanzee was infused with
one dose of a mixture of human monoclonal antibodies 9H9 and 4-7B
(antibodies against hepatitis B virus surface antigen; HBsAg). Blood
samples were taken before and up to 3 weeks after infusion. HBsAg and
antibodies against HBsAg (anti-HBs) were quantified by radioimmunoassay
and enzyme immunoassay. Free anti-HBs was never detected. Thirty min after
the start of the infusion the HBsAg level was minimal with maximum loading
of the chimpanzee HBsAg with human immunoglobulin. HBsAg complexes could
be dissociated by acid treatment. The HBsAg level was completely restored
on day 7. Similar results were obtained for the preS1-containing particles
that may represent the infectious viral particles in the chimpanzee serum.
A mouse monoclonal anti-HBs (HBs.OT40) was found to compete with 9H9 in
artificial immune complexes with the pre-treatment HBsAg from the
chimpanzee. Used as a conjugate, HBs.OT40 yielded a maximum decrease in
the signal in the 30 min sample compared to non-competing anti-HBs
conjugates. This indicates binding of HBsAg with 9H9 in the circulation of
the chimpanzee. Immune-complexed 4-7B could not be detected by its
corresponding 4-7B peptide conjugate, probably due to its low
concentration in the complexes. It is concluded that human monoclonal
anti-HBs can effectively reduce the level of HBsAg in serum from this
chronic carrier. Monoclonals 9H9 and 4-7B may complement each other due to
their different mechanisms of inactivation, probably with higher
efficiency than that monitored by our HBsAg screening assays
