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The
Emergence of Hepatitis B Surface Antigen
Mutants and Their Impact on Diagnostic
Detection.
Paul Coleman and Akhtar Ali.
Abbott Laboratories,
Infectious Disease
Core R&D,
Abbott Park,
IL 60064 USA.
Introduction: Hepatitis B viral mutants
can emerge in patients as a response to
viral treatment options. Hepatitis B
vaccination for example can induce an
immune selection pressure that leads to
the emergence of hepatitis B surface
antigen (HBsAg) mutants. Mutation within
the “a” determinant epitopes of HBsAg
allows the mutant virus to escape
recognition by a neutralizing immune
response and to continue to replicate.
These mutated HBsAg epitopes are also
not recognized by the monoclonal
reagents of some HBsAg diagnostic assays
and therefore present as false negative
results. The mutation position and the
type of mutation impacts HBsAg assay
performance.
Methods: Working from a published model
of HBsAg structure, we investigated
single point, multiple point, and
insertion mutations in the HBsAg amino
acid sequence and their effect on the
binding of several high avidity
monoclonal antibodies.
Results: Four conformational epitopes
were identified in the HBsAg “a”
determinant. Epitope 1 was found between
amino acids 121-124, while Epitope 2 was
found between positions 139-147.
Epitopes 3 and 4 bridge these loop
structures.
Conclusions: As HBsAg mutants will
continue to emerge in response to
selection pressures, an understanding of
immunoassay reactivity with HBsAg
mutants is key to establishing an
appropriate testing algorithm for HBV
detection programs. Epitope mapping of
anti-HBs monoclonal reagents is one tool
to utilize in analyzing immunoassay
reactivity. This approach allows the
selection of immunoassay reagents that
recognize a broad range of HBsAg mutants
and wild-type antigen with a high degree
of sensitivity.
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