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Group A streptococcal vaccines: paving a path for accelerated development.
[acute rheumatic fever]
Group
A
streptococci
(
GAS
)
are
important
causes
of
morbidity
and
mortality
worldwide
.
These
organisms
cause
a
wide
spectrum
of
disease
,
ranging
from
uncomplicated
sore
throat
to
invasive
,
life-threatening
infections
,
as
well
as
immune
complications
such
as
acute
rheumatic
fever
(
ARF
)
,
rheumatic
heart
disease
(
RHD
)
and
acute
post-streptococcal
glomerulonephritis
(
APSGN
)
.
Vaccine
prevention
of
GAS
infections
and
their
immunological
complications
has
been
a
goal
of
researchers
for
decades
.
Several
vaccine
candidates
against
GAS
infection
are
in
various
stages
of
pre-clinical
and
clinical
development
,
including
M
protein-based
vaccines
(
N-
terminal
vaccine
candidates
and
M
protein
conserved
region
vaccines
)
,
and
non-
M
protein
vaccine
candidates
representing
conserved
GAS
antigens
.
Some
of
the
obstacles
to
GAS
vaccine
development
are
related
to
the
complexity
of
the
global
epidemiology
of
GAS
infections
,
the
limitation
in
the
criteria
for
selection
of
antigens
to
include
in
combination
vaccines
as
well
as
the
issues
around
autoimmunity
and
vaccine
safety
,
among
others
.
Overcoming
these
obstacles
will
require
collaborative
efforts
to
develop
innovative
strategies
that
address
key
steps
in
the
pre-clinical
and
clinical
development
process
,
as
well
as
clearly
defining
the
global
burden
of
GAS
diseases
and
the
molecular
epidemiology
of
infections
.
Specific
recommendations
are
presented
for
an
accelerated
plan
leading
to
the
introduction
of
a
broadly
protective
vaccine
designed
for
deployment
in
low
-
,
middle
-
,
and
high
-income
countries
.
Diseases
Validation
Diseases presenting
"global burden"
symptom
acute rheumatic fever
allergic bronchopulmonary aspergillosis
congenital toxoplasmosis
dracunculiasis
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