Biology Reference
In-Depth Information
Immune Responses to Chimeric HEV-VLPs
through Oral Administration
Since many pathogenic viruses and bacteria establish their initial infec-
tions through the mucosal surface, vaccine strategies that can stimulate
mucosal immunity have been widely studied (reviewed in Ogra
et al
.).
19
However, there are several difficulties in oral immunization with non-
replicating molecules, such as low pH in the stomach, presence of pro-
teolytic enzymes in the digestive tract, and presence of physical as well
as biochemical barriers associated with the mucosal surface itself.
19
We
previously reported that the HEV-VLP preserved original HEV con-
struction and entered the epithelial cells of the small intestine by oral
administration.
20
From these findings, mice were immunized with 50
g
of purified VLP-52C by the oral route four times at two-week intervals,
with the mice having the ability to induce mucosal and systemic epi-
tope-specific antibody responses. Specific IgG antibodies to the tag as
well as to HEV were detected in intestinal fluids as early as two wpi
(Fig. 6A). IgG levels in intestinal fluids continued to increase until the
termination of the experiments. Specific IgA to both the tag and HEV
also appeared in intestinal fluids from two wpi, paralleling the IgG lev-
els (Fig. 6B). The IgA levels also continued to increase until the termi-
nation of experiments. As expected, the control mice immunized with
VLP without the tag developed IgG and IgA only to HEV. In sera, lev-
els of a specific IgG antibody to both the tag and HEV showed slightly
higher OD values than those in non-immunized controls, but they never
reached significant levels, as occurred in the intestinal fluids (Fig. 6C).
The levels of specific IgA in sera were also low, although the OD values
were also higher than the non-immunized controls (Fig. 6D). The con-
trol mice immunized with VLP without the tag showed similarly low
OD values to HEV. The specific antibodies in the intestinal fluids were
analyzed for their isotypes at 10 wpi. At this point, average OD values
and SD for IgG and IgA in the intestinal fluids were 1.02
µ
±
0.22 and
0.64
0.040, respectively, to HEV
and the tag in three mice immunized with the chimeric VLP. In the
control mice immunized with VLP without the tag, the average OD
values and SD for IgG and IgA were 0.88
±
0.038, and 0.96
±
0.086 and 0.66
±
±
0.047 and 0.64
±
0.027, and
0.11
±
0.024 and 0.084
±
0.013, respectively, to HEV and the tag. All
