Schistosomiasis
threatens
hundreds
of
millions
people
worldwide.
The
larval
stage
Schistosoma
mansoni
migrates
through
the
lung
and
adult
worms
reside
adjacent
to
colonic
mucosa.
Several
candidate
vaccines
are
in
preclinical
development,
but
none
is
designed
elicit
both
systemic
mucosal
responses.
We
have
repurposed
an
attenuated
Salmonella
enterica
Typhimurium
strain
(YS1646)
express
Cathepsin
B
(CatB),
a
digestive
enzyme
important
for
juvenile
stages
S.
life
cycle.
Previous
studies
demonstrated
prophylactic
therapeutic
efficacy
our
plasmid-based
vaccine.
Here,
we
generated
chromosomally
integrated
(CI)
YS1646
strains
that
CatB
produce
viable
vaccine
eventual
human
use
(stability,
no
antibiotic
resistance).
6-8-week-old
C57BL/6
mice
were
vaccinated
multimodal
oral
(PO)
intramuscular
(IM)
regimen,
then
sacrificed
3
weeks
later.
PO
+
IM
group
had
significantly
higher
anti-CatB
IgG
titers
with
greater
avidity
mounted
significant
intestinal
IgA
responses
compared
PBS
control
(all
P
<
0.0001).
Multimodal
vaccination
balanced
TH1/TH2
humoral
cellular
immune
Production
IFNγ
by
CD4+
CD8+
T
cells
was
confirmed
flow
cytometry
(P
0.0001
&
0.01).
reduced
worm
burden
80.4%,
hepatic
egg
counts
75.2%,
78.4%
A
stable
safe
has
activity
would
be
ideal
conjunction
praziquantel
mass
treatment
campaigns.
Frontiers in Pharmacology,
Год журнала:
2024,
Номер
15
Опубликована: Июль 15, 2024
Graphical
Abstract
Sincere
gratitude
to
Prof.
Jennifer
Keiser
for
generously
granting
permission
the
use
of
tegument
picture
in
this
graphical
abstract.
Vaccine,
Год журнала:
2024,
Номер
unknown, С. 126020 - 126020
Опубликована: Июль 1, 2024
Schistosomiasis
is
caused
by
parasitic
flatworms
(Schistosoma).
The
disease
in
humans
can
be
seven
different
species
of
Schistosoma:
S.
mansoni,
japonicum,
haematobium,
malayensis,
mekongi,
guineensis
and
intercalatum,
as
well
hybrids
between
species,
including
livestock
schistosome
species.
People
are
infected
when
exposed
to
infested
water
the
parasite
larvae
penetrate
skin.
Poor
rural
communities
typically
most
affected,
general
population
who
lives
affected
areas
contaminated
at
risk.
Areas
with
poor
access
safe
adequate
sanitation
also
heightened
About
236.6
million
people
required
treatment
for
schistosomiasis
2019—mostly
living
poor,
communities,
especially
fishing
agricultural
communities.
This
'Vaccine
Value
Profile'
(VVP)
intended
provide
a
high-level,
holistic
assessment
information
data
that
currently
available
inform
potential
public
health,
economic,
societal
value
pipeline
vaccines
vaccine-like
products.
VVP
was
developed
working
group
subject
matter
experts
from
academia,
non-profit
organizations,
private
partnerships,
multi-lateral
organizations.
All
contributors
have
extensive
expertise
on
various
elements
collectively
aimed
identify
current
research
knowledge
gaps.
using
only
existing
publicly
information.
Frontiers in Molecular Biosciences,
Год журнала:
2023,
Номер
10
Опубликована: Апрель 4, 2023
Schistosomiasis
is
a
globally
prevalent,
debilitating
disease
that
poorly
controlled
by
chemotherapy
and
for
which
no
vaccine
exists.
While
partial
resistance
in
people
may
develop
over
time
with
repeated
infections
treatments,
some
animals,
including
the
brown
rat
(Rattus
norvegicus),
are
only
semi-permissive
have
natural
protection.
To
understand
basis
of
this
protection,
we
explored
nature
immune
response
to
infection
Schistosoma
mansoni.
Infection
leads
production
IgG
parasite
glycoproteins
complex-type
N-glycans
contain
non-mammalian-type
modification
core
α2-Xylose
α3-Fucose
(core
Xyl/Fuc).
These
epitopes
expressed
on
surfaces
schistosomula
adult
worms.
Importantly,
these
can
kill
complement-dependent
process
vitro.
Additionally,
sera
from
both
infected
rhesus
monkey
were
capable
killing
manner
inhibited
glycopeptides
containing
Xyl/Fuc.
results
demonstrate
protective
antibodies
schistosome
rats
monkeys
include
responses
Xyl/Fuc
surface-expressed
N-glycans,
raise
potential
novel
glyco-based
vaccines
might
be
developed
combat
disease.
Schistosomiasis
threatens
hundreds
of
millions
people
worldwide.
The
larval
stage
Schistosoma
mansoni
migrates
through
the
lung
and
adult
worms
reside
adjacent
to
colonic
mucosa.
Several
candidate
vaccines
are
in
preclinical
development,
but
none
is
designed
elicit
both
systemic
mucosal
responses.
We
have
repurposed
an
attenuated
Salmonella
enterica
Typhimurium
strain
(YS1646)
express
Cathepsin
B
(CatB),
a
digestive
enzyme
important
for
juvenile
stages
S.
life
cycle.
Previous
studies
demonstrated
prophylactic
therapeutic
efficacy
our
plasmid-based
vaccine.
Here,
we
generated
chromosomally
integrated
(CI)
YS1646
strains
that
CatB
produce
viable
vaccine
eventual
human
use
(stability,
no
antibiotic
resistance).
6-8-week-old
C57BL/6
mice
were
vaccinated
multimodal
oral
(PO)
intramuscular
(IM)
regimen,
then
sacrificed
3
weeks
later.
PO
+
IM
group
had
significantly
higher
anti-CatB
IgG
titers
with
greater
avidity
mounted
significant
intestinal
IgA
responses
compared
PBS
control
(all
P
<
0.0001).
Multimodal
vaccination
balanced
TH1/TH2
humoral
cellular
immune
Production
IFNγ
by
CD4+
CD8+
T
cells
was
confirmed
flow
cytometry
(P
0.0001
&
0.01).
reduced
worm
burden
80.4%,
hepatic
egg
counts
75.2%,
78.4%
A
stable
safe
has
activity
would
be
ideal
conjunction
praziquantel
mass
treatment
campaigns.
