Journal of Medical Virology,
Год журнала:
2024,
Номер
97(1)
Опубликована: Дек. 26, 2024
ABSTRACT
The
outbreak
of
clade
II
monkeypox
virus
(MPXV)
and
the
additional
in
Central
Africa
I
from
2023
have
attracted
worldwide
attention.
development
a
scalable
effective
vaccine
against
ongoing
epidemic
mpox
is
urgently
needed.
We
previously
constructed
two
bivalent
MPXV
mRNA
vaccines,
LBA
(B6R‐A29L)
LAM
(A35R‐M1R),
quadrivalent
vaccine,
LBAAM
(B6R‐A35R‐A29L‐M1R).
These
vaccines
at
20
µg
dose
could
induce
potential
antigen‐specific
immune
responses
provide
protection
lethal
VACV
challenge.
Compared
with
individual
LBA&
displayed
superior
protective
effects.
To
characterize
these
further,
we
monitored
long‐term
immunity
as
long
28
weeks
after
initial
immunization
optimized
dosages
to
decrease
cost
production
for
future
clinical
use.
Our
results
demonstrated
that
both
(A35R‐M1R)
tetravalent
elicit
long‐lasting
IgG
antibodies
well
neutralizing
MPXV.
They
all
provided
complete
challenge
until
post
prime
immunization.
Moreover,
immunogenicity
efficacy
(LBAAM
LAM)
are
dependent,
even
low‐dose
(1
µg)
sufficient
valuable
clues
further
use
humans.
Nature Communications,
Год журнала:
2025,
Номер
16(1)
Опубликована: Март 26, 2025
The
persistent
monkeypox
outbreaks
intensify
the
demand
for
vaccines.
Based
on
mRNA
vaccine
platform,
we
conduct
a
systematic
screening
of
virus
(MPXV)
surface
proteins
from
two
types
viral
particles,
extracellular
enveloped
viruses
(EVs)
and
intracellular
mature
(MVs).
This
unveils
12
important
antigens
with
diverse
levels
neutralizing
immunogenicity.
Further
assessment
reveals
that
combinations
4,
8,
these
antigens,
namely
Mix-4,
Mix-8,
Mix-12,
induce
varying
degrees
immune
protection,
Mix-12
being
most
potent.
finding
demonstrates
significance
not
only
level
but
also
diversity
antibodies
in
providing
potent
protection.
Additionally,
utilize
T
cell-epitope
enrichment
strategy,
analyzing
complete
proteome
sequence
MPXV
to
predict
antigenic
epitope-rich
regions.
Integration
regions
into
cellular
immune-targeting
antigen,
named
MPX-EPs,
showcases
can
independently
confer
Furthermore,
co-immunization
MPX-EPs
achieves
protection
against
challenge.
Overall,
results
suggest
an
effective
approach
enhance
vaccines
through
specific
coordination
humoral
responses.
immunogenicity
screen
proteins,
authors
develop
which
they
combine
cell
achieve
coordinated
activation
International Journal of Molecular Sciences,
Год журнала:
2025,
Номер
26(7), С. 3055 - 3055
Опубликована: Март 26, 2025
Non-coding
RNAs
(ncRNAs)
are
a
class
of
that
largely
lack
the
capacity
to
encode
proteins.
They
have
garnered
significant
attention
due
their
central
regulatory
functions
across
numerous
cellular
and
physiological
processes
at
transcriptional,
post-transcriptional,
translational
levels.
Over
past
decade,
ncRNA-based
therapies
gained
considerable
in
diagnosis,
treatment,
prevention
diseases,
many
studies
revealed
relationship
between
ncRNAs
diseases.
At
same
time,
tissue
specificity,
an
increasing
number
projects
focused
on
application
as
biomarkers
well
design
development
novel
vaccines
for
clinical
use.
These
may
also
drive
research
into
potential
molecular
mechanisms
complex
pathogenesis
related
However,
new
need
be
validated
effectiveness.
Additionally,
produce
safe
stable
RNA
products,
factors
such
purity,
precise
dosage,
effective
delivery
methods
must
ensured
achieve
optimal
bioactivity.
challenges
remain
key
issues
ncRNAs.
This
review
summarizes
prospects
biomarkers,
current
status
applications
vaccines,
discusses
expectations
disease
diagnosis
drug
therapy.
Frontiers in Immunology,
Год журнала:
2025,
Номер
16
Опубликована: Март 31, 2025
Porcine
Epidemic
Diarrhea
Virus
(PEDV)
and
Transmissible
Gastroenteritis
(TGEV)
pose
significant
threats
to
neonatal
piglets,
leading
severe
diarrhea
potentially
lethal
consequences.
Beyond
enforcing
stringent
biosecurity
protocols,
effective
safe
vaccinations
are
crucial
in
mitigating
the
impact
of
these
diseases.
In
this
study,
PEDV
S1
(PS1)
TGEV
(TS1)
antigens
were
initially
chosen
as
candidates
for
development
circRNA
vaccines.
Recognizing
comparatively
lower
immunogenicity
PS1
antigen
contrast
TS1
antigen,
we
strategically
conjugated
with
pig
fragment
crystallizable
(Fc)
region
form
PS1F.
Despite
efforts,
bivalent
vaccine
prepared
using
an
equal
amount
circRNAPS1F
circRNATS1
mixture
still
led
a
reduction
antibody
levels
against
PS1.
Subsequent
dosage
optimization
two
vaccines
resulted
induction
comparable
specific
antibodies
T
cell
immunity.
Furthermore,
sequential
vaccination
regimen
commercial
inactivated
(IAV)
could
elicit
predominantly
Th1-driven
responses
effectively
neutralize
both
TGEV.
Our
findings
not
only
provide
potential
strategy
or
multivalent
circRNA/mRNA-based
but
also
highlight
promising
application
strategies
within
swine
industry.
Frontiers in Immunology,
Год журнала:
2025,
Номер
16
Опубликована: Апрель 11, 2025
Introduction
The
remarkable
commercial
success
of
mRNA
vaccines
against
COVID-19
and
tumors,
along
with
their
potential
as
therapeutic
drugs,
has
significantly
boosted
enthusiasm
for
circular
RNAs
(circRNA)
a
promising
next-generation
platform.
development
novel
circRNA
cyclization
technologies
represents
significant
leap
forward
in
RNA
engineering
applications.
Recent
advancements
group
I
IIB
self-splicing
intron-based
ribozymes
have
enabled
precise
molecules.
However,
this
approach
faces
limitations,
including
low
efficiency
the
requirement
additional
additives,
which
restrict
its
broader
application.
Group
IIC
introns
represent
shortest
known
selfsplicing
employ
splicing
mechanism
that
is
fundamentally
distinct
from
introns.
to
carry
exogenous
sequences
RNA-based
platforms
remains
an
open
question
warrants
further
investigation.
Methods
Here,
we
demonstrate
can
efficiently
circularize
express
proteins
varying
lengths,
evidenced
by
luciferase
GFP
reporter
systems.
Leveraging
structural
biology-based
design,
engineered
RSV
pre-F
protein
validated
vaccine
platform
preventing
infectious
diseases.
Results
In
mouse
models,
nucleic
acid
developed
using
elicited
superior
immunogenicity
vivo
protective
efficacy
compared
protein-adjuvant
vaccines.
Discussion
holds
promise
advancing
therapeutics
disease
treatment
prevention.
Pathogens,
Год журнала:
2024,
Номер
13(8), С. 692 - 692
Опубликована: Авг. 15, 2024
Engineered
circular
RNAs
(circRNAs)
are
a
class
of
single-stranded
with
head-to-tail
covalently
linked
structures
that
integrate
open
reading
frames
(ORFs)
and
internal
ribosome
entry
sites
(IRESs)
the
function
coding
expressing
proteins.
Compared
to
mRNA
vaccines,
circRNA
vaccines
offer
more
improved
method
is
safe,
stable,
simple
manufacture.
With
rapid
revelation
biological
functions
success
Severe
Acute
Respiratory
Coronavirus
Type
II
(SARS-CoV-2)
biopharmaceutical
companies
researchers
around
globe
attempting
develop
stable
for
illness
prevention
treatment.
Nevertheless,
research
on
still
in
its
infancy,
work
assessment
needed
their
synthesis,
delivery,
use.
In
this
review,
based
current
understanding
molecular
properties
immunotherapeutic
mechanisms
circRNA,
we
summarize
preparation
methods
including
design,
purification,
identification.
We
discuss
delivery
strategies
challenges
facing
clinical
application
circRNAs
provide
references
vaccine-related
research.
bioRxiv (Cold Spring Harbor Laboratory),
Год журнала:
2024,
Номер
unknown
Опубликована: Авг. 27, 2024
Abstract
Recent
advances
in
vaccine
technology
have
positioned
messenger
RNA
(mRNA)
vaccines
as
safe
and
reliable
options
for
human
use.
Conventionally,
mRNA
were
designed
using
linear
or
self-amplifying
(SAM),
the
latter
considered
to
be
superior.
However,
limited
success
was
achieved
with
SAM
during
COVID-19
pandemic.
Further,
studies
on
Circular
(Circ-RNA)
against
SARS-CoV-2,
Ebola
monkey
pox
proved
their
efficacy.
Circ-RNAs
are
highly
stable,
neither
they
induce
inflammatory
response
nor
require
any
extracellular
protein
function.
Here,
we
compared
efficacy
of
SAM-
Circ-RNA
SARS-CoV-2-RBD
(receptor
binding
domain)
antigen.
Both
SAM-RBD
Circ-RBD
induced
a
comparable
anti-RBD
IgG
titer
virus-neutralizing
antibody
titer.
significantly
higher
memory
T-cell
response.
Immunization
showed
no
mortality
improved
lung
pathophysiology
acute
SARS-CoV-2
infection
mice.
The
is
stable
4
weeks
at
0
C.
A
bivalent
containing
both
delta
omicron
variants
potently
neutralized
these
viruses.
These
findings
demonstrate
Circ-RNA-RBD
an
excellent
candidate
also
provide
platform
developing
candidates
other
viruses
rapidly
emerging
variants.
bioRxiv (Cold Spring Harbor Laboratory),
Год журнала:
2024,
Номер
unknown
Опубликована: Ноя. 22, 2024
Abstract
mRNA-based
in
vivo
CAR
T
cell
engineering
offers
advantages
over
ex
therapies,
including
streamlined
manufacturing
and
transient
expression.
However,
current
delivery
requires
antibody-modified
vehicles
with
challenges.
In
this
study,
inspired
by
cardiolipin,
we
identified
a
cardiolipin-like
di-phosphoramide
lipid
that
improved
transfection
without
targeting
ligands,
both
vitro.
The
cell-favored
tropism
is
likely
due
to
the
lipid’s
packing,
shape,
rigidity.
Encapsulating
circular
RNA
further
prolonged
mRNA
expression
spleen
cells.
Using
PL40
nanoparticles,
delivered
encoding
senolytic
inflammatory
antigen
urokinase-type
plasminogen
activator
receptor
(uPAR),
alleviating
uPAR-related
liver
fibrosis
rheumatoid
arthritis
(RA).
Single
sequencing
humans
confirmed
uPAR’s
relevance
senescence
inflammation
RA.
To
enhance
clinical
translation,
screened
humanized
scFvs
against
uPAR,
establishing
human
uPAR
CAR,
potential
for
treating
aging-inflamed
disorders.
One
Sentence
Summary
We’ve
developed
unique
class
of
Cardiolipin-mimic
lipids
facilitate
cells
need
antibody
modification,
enhancing
treatment
through
propelling
application
uPAR.
Journal of Medical Virology,
Год журнала:
2024,
Номер
97(1)
Опубликована: Дек. 26, 2024
ABSTRACT
The
outbreak
of
clade
II
monkeypox
virus
(MPXV)
and
the
additional
in
Central
Africa
I
from
2023
have
attracted
worldwide
attention.
development
a
scalable
effective
vaccine
against
ongoing
epidemic
mpox
is
urgently
needed.
We
previously
constructed
two
bivalent
MPXV
mRNA
vaccines,
LBA
(B6R‐A29L)
LAM
(A35R‐M1R),
quadrivalent
vaccine,
LBAAM
(B6R‐A35R‐A29L‐M1R).
These
vaccines
at
20
µg
dose
could
induce
potential
antigen‐specific
immune
responses
provide
protection
lethal
VACV
challenge.
Compared
with
individual
LBA&
displayed
superior
protective
effects.
To
characterize
these
further,
we
monitored
long‐term
immunity
as
long
28
weeks
after
initial
immunization
optimized
dosages
to
decrease
cost
production
for
future
clinical
use.
Our
results
demonstrated
that
both
(A35R‐M1R)
tetravalent
elicit
long‐lasting
IgG
antibodies
well
neutralizing
MPXV.
They
all
provided
complete
challenge
until
post
prime
immunization.
Moreover,
immunogenicity
efficacy
(LBAAM
LAM)
are
dependent,
even
low‐dose
(1
µg)
sufficient
valuable
clues
further
use
humans.
