Abstract:
This study aims to characterize the antigenicity of the Capsid (C) protein and the human
antibody responses to C protein from the four dengue virus (DENV) serotypes. Parker
hydrophilicity prediction, Emini surface accessibility prediction and Karplus & Schulz flexibility
predictions were used to bioinformatically characterize antigenicity. The human antibody
response to C protein was assessed by ELISA using immune sera and an array of overlapping
DENV2 C peptides. DENV2 C protein peptides P1 (located on C protein at 2±18 a.a),
P11 (79±95 a.a) and P12 (86±101 a.a) were recognized by most individuals exposed to
infections with only one of the 4 DENV serotypes as well as people exposed to infections
with two serotypes. These conserved peptide epitopes are located on the amino (1±40 a.a)
and carboxy (70±100 a.a) terminal regions of C protein, which were predicted to be antigenic
using different bioinformatic tools. DENV2 C peptide P6 (39±56 a.a) was recognized by all
individuals exposed to DENV2 infections, some individuals exposed to DENV4 infections
and none of the individuals exposed to DENV1 or 3 infections. Thus, unlike C peptides P1,
P11 and P12, which contain epitopes, recognized by DENV serotype cross-reactive antibodies,
DENV2 peptide P6 contains an epitope that is preferentially recognized by antibodies
in people exposed to this serotype compared to other serotypes. We discuss our results
in the context of the known structure of C protein and recent work on the human B-cell
response to DENV infection.
