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A vaccine against Streptococcus pyogenes: the potential to prevent rheumatic fever and rheumatic heart disease.
[acute rheumatic fever]
Streptococcus
pyogenes
causes
severe
,
invasive
infections
such
as
the
sequelae
associated
with
acute
rheumatic
fever
,
rheumatic
heart
disease
,
acute
glomerulonephritis
,
uncomplicated
pharyngitis
,
and
pyoderma
.
Efforts
to
produce
a
vaccine
against
S
.
pyogenes
began
several
decades
ago
,
and
different
models
have
been
proposed
.
We
have
developed
a
vaccine
candidate
peptide
,
StreptInCor
,
comprising
55
amino
acid
residues
of
the
C-
terminal
portion
of
the
M
protein
and
encompassing
both
the
T
-
and
B-
cell
protective
epitopes
.
The
present
article
summarizes
data
from
the
previous
5
years
during
which
we
tested
the
immunogenicity
and
safety
of
StreptInCor
in
different
animal
models
.
We
showed
that
StreptInCor
overlapping
peptides
induced
cellular
and
humoral
immune
responses
of
individuals
bearing
different
HLA
class
II
molecules
.
These
results
are
consistent
with
peptides
that
have
a
universal
vaccine
epitope
.
The
tridimensional
molecular
structure
of
StreptInCor
was
elucidated
by
nuclear
magnetic
resonance
spectroscopy
,
which
showed
that
its
structure
is
composed
of
two
microdomains
linked
by
an
18
-
residue
α-
helix
.
Additionally
,
we
comprehensively
evaluated
the
structural
stability
of
the
StreptInCor
peptide
in
different
physicochemical
conditions
using
circular
dichroism
.
Additional
experiments
were
performed
with
inbred
,
outbred
,
and
HLA
class
II
transgenic
mice
.
Analysis
of
several
organs
of
these
mice
showed
neither
deleterious
nor
autoimmune
reactions
even
after
a
long
period
of
vaccination
,
indicating
that
the
StreptInCor
candidate
peptide
could
be
considered
as
an
immunogenic
and
safe
vaccine
.
Diseases
Validation
Diseases presenting
"long period"
symptom
acute rheumatic fever
aromatase deficiency
hydrocephalus with stenosis of the aqueduct of sylvius
locked-in syndrome
lymphangioleiomyomatosis
oral submucous fibrosis
waldenström macroglobulinemia
well-differentiated liposarcoma
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