Monkeypox
(MPOX)
is
a
zoonotic
disease
caused
by
Orthopoxvirus
monkeypox
(MPXV),
belonging
to
the
genus,
and
exhibits
symptoms
similar
smallpox.
In
2024,
outbreak
in
Democratic
Republic
of
Congo
continued
develop,
raising
widespread
global
public
health
concerns.
September
2023,
first
local
was
reported
Nantong,
Jiangsu
Province,
China.
Whole-genome
sequencing
samples
from
seven
confirmed
patients
identified
new
lineage,
C.1.1,
which
may
be
related
imported
cases
Japan.
Evolutionary
analysis
MPXV
showed
fewer
mutations
mediated
Apolipoprotein
B
mRNA
Editing
Catalytic
polypeptide-like
3
(APOBEC3).
Additionally,
N2L
protein
disrupted
transcription
initiation,
while
changes
Cytomegalovirus-encoded
immunomodulatory
(CrmB)
led
structural
instability
protein.
It
hoped
that
these
findings
will
provide
insights
for
future
research
on
evolutionary
mechanisms
virus
development
vaccines.
Vaccines,
Год журнала:
2025,
Номер
13(5), С. 471 - 471
Опубликована: Апрель 27, 2025
Monkeypox,
twice
declared
a
public
health
emergency
of
international
concern
by
the
WHO,
currently
lacks
approved
targeted
therapeutics.
This
study
focused
on
development
monkeypox
virus
(MPXV)
E8-specific
human
monoclonal
antibodies
(mAbs)
derived
from
recipients
recombinant
vaccinia
vaccine
(rTV),
with
subsequent
evaluation
their
cross-neutralizing
activity
against
orthopoxviruses,
including
(VACV)
and
MPXV.
Three
mAbs
(C5,
C9,
F8)
were
isolated
rTV
vaccinees.
Structural
mapping
characterized
binding
domains
MPXV
E8
VACV
D8
proteins.
Neutralization
potency
was
assessed
TianTan
strain
clade
IIb.
A
combo
further
evaluated
in
VACV-infected
mice
model
for
clinical
recovery
viral
load
reduction.
Complement-dependent
enhancement
mechanisms
also
investigated
vitro.
C9
targets
virion
surface
region
both
intravirion
D8,
showing
cross-neutralization
(IC50
=
3.0
μg/mL)
51.1
ng/mL)
All
three
demonstrated
potent
neutralization
vitro:
C5
3.9
ng/mL),
F8
101.1
ng/mL).
Notably,
complement
enhanced
>50-fold,
although
no
observed
In
vivo
administration
accelerated
24
h
achieved
significant
clearance
(0.9-log
reduction).
E8-targeting
exhibited
broad-spectrum
demonstrating
therapeutic
potential
historical
emerging
pathogens.
However,
MPXV's
resistance
to
complement-dependent
highlights
necessity
pathogen-adapted
optimization.
These
findings
establish
as
critical
conserved
target
pan-poxvirus
countermeasure
development.
Vaccines,
Год журнала:
2024,
Номер
13(1), С. 27 - 27
Опубликована: Дек. 31, 2024
Available
assays
to
measure
pox
virus
neutralizing
antibody
titers
are
laborious
and
take
up
5
days.
In
addition,
T
cell
responses
require
the
use
of
specific
antigens,
which
may
not
be
same
for
all
viruses.
This
study
reports
development
robust
measurement
mpox-specific
antibodies
IFN-γ-producing
T-cell
responses.
Fourteen
samples
from
7
volunteers
who
received
Modified
Vaccinia
Ankara-Bavarian
Nordic
(MVA-BN)
were
used.
The
focused
reduction
neutralization
test
(FRNT)
was
performed
using
A29
monoclonal
antibody.
Optimization
further
FRNT
conducted
plaque
(PRNT)
as
gold
standard.
IFN-γ
ELISPOT
assay
optimized
different
mpox
antigen
preparations.
Results
with
pre-vaccination
compared
post-vaccination
Wilcoxon
matched-pairs
test.
Pre-vaccination
sera
(n
=
7)
had
FRNT50
(i.e.,
that
inhibited
at
least
50%
virus)
109.1
±
161.8
303.7
402.8
(mean
SD),
respectively.
Regression
analysis
fold
changes
in
PRNT50
showed
two
closely
agree
25
tests
on
paired
samples,
R2
0.787).
Using
UV-inactivated
an
antigen,
number
spot-forming
cells
(SFC)
(16.13
15.86,
mean
SD)
significantly
lower
than
SFC
(172.9
313.3,
p
0.0078.
Our
newly
developed
microneutralization
has
a
good
correlation
PRNT.
is
appropriate
measures
cross-reactive
cells.
These
will
useful
future
vaccine
studies.
