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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
"fever"
symptom
22q11.2 deletion syndrome
acute rheumatic fever
alexander disease
allergic bronchopulmonary aspergillosis
canavan disease
carcinoma of the gallbladder
child syndrome
congenital toxoplasmosis
cushing syndrome
cystinuria
dracunculiasis
erdheim-chester disease
esophageal adenocarcinoma
esophageal carcinoma
familial mediterranean fever
focal myositis
hodgkin lymphoma, classical
lamellar ichthyosis
legionellosis
locked-in syndrome
malignant atrophic papulosis
neonatal adrenoleukodystrophy
neuralgic amyotrophy
oculocutaneous albinism
papillon-lefèvre syndrome
pyomyositis
pyruvate dehydrogenase deficiency
scrub typhus
severe combined immunodeficiency
sneddon syndrome
systemic capillary leak syndrome
triple a syndrome
typhoid
waldenström macroglobulinemia
wolf-hirschhorn syndrome
This symptom has already been validated