Organoids,
Journal Year:
2024,
Volume and Issue:
3(1), P. 18 - 31
Published: Feb. 1, 2024
Existing
mRNA
COVID-19
vaccines
have
shown
efficacy
in
reducing
severe
cases
and
fatalities.
However,
their
effectiveness
against
infection
caused
by
emerging
SARS-CoV-2
variants
has
waned
considerably,
necessitating
the
development
of
variant
vaccines.
Ideally,
next-generation
will
be
capable
eliciting
broader
more
sustained
immune
responses
to
effectively
counteract
new
variants.
Additionally,
vitro
assays
that
closely
represent
virus
neutralization
humans
would
greatly
assist
analysis
protective
vaccine-induced
antibody
responses.
Here,
we
present
findings
from
a
VLP
vaccine
encompassing
three
key
structural
proteins:
Spike
(S),
Envelope
(E),
Membrane
(M).
The
produced
neutralizing
antibodies
as
determined
surrogate
test,
induced
virus-specific
T-cell
responses:
predominantly
CD4+,
although
CD8+
T
cell
were
detected.
prominent
with
delivered
AddaVax
compared
alone.
adjuvanted
was
completely
live
challenge
mice.
Furthermore,
utilized
air–liquid-interface
(ALI)-differentiated
human
nasal
epithelium
(HNE)
an
system,
which
authentically
models
neutralization.
We
show
sera
VLP-vaccinated
mice
neutralized
infection,
demonstrating
potential
ALI-HNE
assess
Nab.
Molecular Therapy — Methods & Clinical Development,
Journal Year:
2025,
Volume and Issue:
33(1), P. 101418 - 101418
Published: Jan. 22, 2025
Engineering
of
adeno-associated
virus
(AAV)
capsids
allowed
for
the
development
gene
therapy
vectors
with
improved
tropism
and
enhanced
transduction
efficiency.
Capsid
engineering
can
also
be
used
to
adapt
AAV
technology
applications
outside
therapy.
Here,
we
investigated
modified
as
scaffolds
presentation
large
immunogenic
antigens
elicit
a
strong
specific
immune
response
against
pathogens.
Using
SARS-CoV-2
model
pathogen,
introduced
∼200
amino
acids
receptor-binding
domain
(RBD)
into
surface-exposed
variable
loop
region
AAV2
AAV9,
resulting
in
AAV2.RBD
AAV9.RBD
(AAV.RBDs).
This
endowed
AAV.RBDs
SARS-CoV-2-like
properties,
such
angiotensin-converting
enzyme
2
receptor
affinity.
In
line
this,
were
neutralized
by
sera
from
human
donors
vaccinated
SARS-CoV-2.
When
administered
subcutaneously
rabbits,
elicited
humoral
RBD.
Moreover,
able
trigger
RBD-specific
cellular
responses
peripheral
lymphocytes.
conclusion,
this
novel
AAV-based
next-generation
vaccine
platform
allows
antigenic
sequences
responses.
versatile
could
explored
context
diseases
where
conventional
immunization
approaches
have
been
unsuccessful.
Cell Death and Differentiation,
Journal Year:
2025,
Volume and Issue:
unknown
Published: Feb. 28, 2025
Abstract
Excessive
inflammation
and
cytokine
release
are
hallmarks
of
severe
COVID-19.
Certain
programmed
cell
death
processes
can
drive
inflammation,
however,
their
role
in
the
pathogenesis
COVID-19
is
unclear.
Pyroptosis
a
pro-inflammatory
form
regulated
initiated
by
inflammasomes
executed
pore-forming
protein
gasdermin
D
(GSDMD).
Using
an
established
mouse
adapted
SARS-CoV-2
virus
panel
gene-targeted
mice
we
found
that
deletion
inflammasome
(NLRP1/3
adaptor
ASC)
pore
forming
proteins
involved
pyroptosis
(GSDMA/C/D/E)
only
marginally
reduced
IL-1β
levels
did
not
impact
disease
outcome
or
viral
loads.
Furthermore,
infection
trigger
GSDMD
activation
lungs.
Finally,
observe
any
difference
between
WT
animals
with
compound
deficiencies
initiator
caspases
(
C1/11/12
−/−
).
This
indicates
classical
canonical
non-canonical
known
to
process
activate
pro-IL-1β,
pro-IL-18
do
substantially
contribute
pathogenesis.
However,
loss
IL-1β,
but
absence
IL-18,
ameliorated
enhanced
survival
infected
compared
wildtype
mice.
Collectively,
these
findings
demonstrate
important
factor
contributing
disease,
its
was
largely
independent
pyroptotic
pathways.
Frontiers in Microbiology,
Journal Year:
2023,
Volume and Issue:
14
Published: June 7, 2023
The
development
of
virus-like
particle
(VLP)
based
vaccines
for
human
papillomavirus,
hepatitis
B
and
E
viruses
represented
a
breakthrough
in
vaccine
development.
However,
dengue
COVID-19,
technical
complications,
such
as
an
incomplete
understanding
the
requirements
protective
immunity,
but
also
limitations
processes
to
manufacture
VLP
enveloped
large
scale,
have
hampered
Selecting
right
adjuvant
is
important
consideration
ensure
that
induces
antibody
T
cell
responses.
For
diseases
like
COVID-19
fever
caused
by
RNA
exist
families
viral
variants
with
potential
escape
vaccine-induced
more
efficacious
necessary.
Here,
we
describe
characterisation
novel
candidates
using
SARS-CoV-2
virus
(DENV),
containing
major
structural
proteins,
protypes
approach
produce
vaccines.
VLPs
were
characterised
Western
immunoblot,
enzyme
immunoassay,
electron
atomic
force
microscopy,
vitro
vivo
immunogenicity
studies.
Microscopy
techniques
showed
proteins
self-assemble
form
authentic
native
viruses.
inclusion
glycolipid
adjuvant,
α-galactosylceramide
(α-GalCer)
formulation
led
high
levels
natural
killer
(NKT)
stimulation
,
strong
memory
CD8
+
responses
demonstrated
SARS-CoV-2,
C
(HCV)
DEN
VLPs.
This
study
shows
our
unique
presents
promising,
much
needed,
new
platform
fight
against
infections
Vaccines,
Journal Year:
2023,
Volume and Issue:
11(3), P. 526 - 526
Published: Feb. 23, 2023
We
previously
developed
a
polysaccharide-–RBD-conjugated
nanoparticle
vaccine
which
induced
protective
efficacy
against
SARS-CoV-2
in
mouse
model.
Here,
we
newly
vaccine,
SCTV01A,
by
chemically
conjugating
recombinant
RBD-Fc
and
PPS14
(Streptococcus
pneumoniae
serotype
type
14
capsular
polysaccharide).
The
immunogenicity
toxicity
of
SCTV01A
were
evaluated
animal
models.
conjugation
enhanced
the
C57BL/6
mice
whether
formulated
with
SCT-VA02B
or
Alum
adjuvant.
also
high
opsonophagocytic
activity
(OPA)
S.
14.
In
addition,
stimulated
potent
neutralizing
titers
rhesus
macaques
effectively
reduced
lung
inflammation
after
infection
neither
antibody-dependent
enhancement
(ADE)
nor
vaccine-enhanced
diseases
(VED)
phenomenon.
Importantly,
long-term
study
did
not
cause
any
abnormal
was
tolerated
at
highest
tested
dose
(120
μg).
existing
toxicological
evaluation
results
have
demonstrated
safety
will
be
promising
feasible
to
protect
infection.
Journal of Medicinal Chemistry,
Journal Year:
2024,
Volume and Issue:
unknown
Published: Dec. 9, 2024
The
controlled
release
of
immunostimulatory
agents
represents
a
promising
strategy
to
enhance
vaccine
efficacy
while
minimizing
side
effects.
This
study
aimed
improve
the
RBD-Fc-based
COVID-19
through
combining
an
iNKT
cell
agonist
and
TLR7/8
using
covalent
conjugation
temporal
delivery.
We
hypothesized
that
these
combinations
would
yield
more
balanced
Th1/Th2
immune
response.
For
conjugation,
we
employed
uncleavable
linker
self-immolative
disulfide
conjugate
α-galactosylceramide
(αGC)
imidazoquinoline
(IMDQ).
αGC-SS-IMDQ-Ac
conjugate,
designed
with
prodrug
for
release,
elicited
higher
IFN-γ/IL-4
T
response
ratio
than
individual
adjuvants
or
their
admixture.
In
delivery
approach,
administering
IMDQ
followed
by
αGC
after
2
h
resulted
in
highest
IgG2a/IgG1
ratio,
significantly
surpassing
other
groups.
A
6
delay
between
glycolipid
injections
yielded
IgG
responses,
enhancing
IgG,
IgG1,
IgG2a
levels
synergistically.
bioRxiv (Cold Spring Harbor Laboratory),
Journal Year:
2023,
Volume and Issue:
unknown
Published: Oct. 4, 2023
Abstract
To
address
the
limitations
of
whole-spike
COVID
vaccines,
we
explored
mRNA
vaccines
encoding
membrane-anchored
receptor-binding
domain
(RBD-TMs),
each
a
fusion
variant
RBD,
transmembrane
(TM)
and
cytoplasmic
tail
(CT)
fragments
SARS-CoV-2
spike
protein.
In
naive
mice,
RBD-TM
against
ancestral
SARS-CoV-2,
Beta,
Delta,
Delta-plus,
Kappa,
Omicron
BA.1
or
BA.5,
all
induced
strong
humoral
responses
target
RBD.
Multiplex
surrogate
viral
neutralization
(sVNT)
assays
indicated
broad
neutralizing
activity
range
RBDs.
setting
heterologous
boost,
background
exposure
to
whole
sVNT
studies
suggested
that
were
able
overcome
detrimental
effects
immune
imprinting.
BA.5
booster
serum
antibodies
with
12
22-fold
higher
RBD
than
their
equivalent
variants.
Boosting
provided
good
protection
more
recent
variants
including
XBB
XBB.1.5.
Each
is
28%
length
its
equivalent.
This
advantage
will
enable
tetravalent
be
developed
at
well-tolerated
doses
formulated
mRNA.
One
Sentence
Summary
RBDs
mutants
are
effective
can
imprinting
in
mice
