Biology Reference
In-Depth Information
also supports the hypothesis that the tag is exposed on the surface,
since an internally localized B cell epitope in chimeric parvovirus-VLP
failed to induce a specific antibody response.
11
Furthermore, this
hypothesis is consistent with the results of three-dimensional analysis
of the Norwalk virus-VLP particle, in which the C-terminal is exposed
to the VLP surface.
26
Considering that B cell epitopes are generally
hydrophilic and most likely exposed to the VLP surface, B cell epitope
regions may not be directly involved in the protein-protein interac-
tions to form a VLP. Our unsuccessful insertions into internal sites
suggest that the integrity of internal regions must be maintained for
proper protein folding and VLP formation. To find potential internal
insertion sites, a precise three-dimensional structural map of the
HEV-VLP may be necessary.
Oral vaccination has obvious advantages for a field trial in a large-
scale public health vaccination program.
27
From a practical stand-
point, oral administration is less stressful for vaccine recipients and
does not require professional skill for administration. Moreover, deliv-
ery of vaccines via the intestinal tract is considered to be inherently
safer than systemic injection. Encouraging results of phase I trials
using Norwalk virus VLPs have recently been reported.
28
We also
confirmed that chimeric HEV-VLPs carrying foreign CTL and B cell
epitope at C-termini can elicit mucosal and systemic cellular immune
responses as well as humoral immune responses by oral administration
(submitted). It has become apparent that mucosal immune responses
on different mucosal surfaces were achieved simultaneously, despite
the initial stimulation of a single mucosal site.
29,30
Therefore, it is
probable that oral administration of chimeric HEV-VLPs stimulates
immune responses simultaneously on distant mucosal surfaces as well.
This phenomenon significantly extends the potential use of chimeric
HEV-VLPs as an oral vaccine vehicle.
A chimeric HEV-VLP has several advantages as an oral vaccine
vector. First, large amounts can be easily obtained from standard cul-
tivation protocols compared with amounts of other VLPs obtained.
Second, the outcome of delivery of vaccine Ag in humans can be pre-
dicted using conventional laboratory animals, since HEV naturally
infects various animals as well as humans through the same infectious
