in vivo

Laboratory for
Vaccine Design
Team leader
Yasuyuki Ishii
Research Scientists : Kenichi Masuda
Showgo Kurata
Yuki Tamura
Technical Staff
Student Trainees
: Annabelle Teng
Haruka Katagiri
Yukiko Takamoto
Risa Nozawa
: Hiroyuki Fujita
Several antigens have been used for
antigen-specific immunotherapy for allergic
diseases, however, the risk of anaphylaxis after
the administration of these antigens has not
been completely excluded. Furthermore, despite
the fact that allergic immunotherapy has been
in clinical practice for decades, the mechanisms
by which such therapy may attenuate allergic
symptoms remain unclear. Since the allergic
reaction in mice is quite different from that of
humans, other suitable animal models have
been sought. Dogs have an allergic reaction
similar to humans and manifest clinical signs of
allergy. Therefore, in terms of clinical evaluation,
the dog is an appropriate model for investigation
of therapeutic efficacy prior to application of any
therapy to humans.
Appropriate antigens for sublingual
immunotherapy (SLIT) for Japanese cedar
pollinosis may be the native cedar pollen
antigens (e.g., proteins such as Cry j1 and Cry
j2). However, the risk of anaphylaxis induced by
these antigens cannot be excluded even with a
mucosal therapy like SLIT. Allergic reactions occur
following binding of the allergen to IgE antibodies
occupying Fcε receptors on the surface of mast
cells, resulting in mast cell degranulation and
release of potent immunological mediators. In
cases where high levels of allergen specific IgE
are bound to mast cells in vital organs, systemic
anaphylaxis can ensue on exposure to even
minute amounts of allergen, resulting in life
threatening bronchconstriction and hypotension.
It is known that most IgE antibodies recognize
conformational epitopes of the antigens, therefore
one could predict that denatured antigens would
show low or no binding to IgE antibodies specific
to the native form of the same antigen. With that in
mind, we prepared a recombinant fusion protein
joining the Cry j1 and Cry j2 proteins in a nonnative
state for use as a possible allergy vaccine.
The aims of this project are: to develop safe
and efficient antigens that can be utilized for SLIT
and to investigate the therapeutic effects of these
reagents on the allergic reaction and its clinical
symptoms in an allergy-prone dog colony with
high basal IgE levels.
Study of the therapeutic efficacy of
sub-lingual immunotherapy (SLIT) for
Japanese cedar pollinosis
Structural genes of mature region encoding
Japanese cedar major antigens, the Cry j1 and
Cry j2 proteins, were fused, and the resultant
78