Vaccines,
Год журнала:
2023,
Номер
11(12), С. 1810 - 1810
Опубликована: Дек. 3, 2023
The
new
SARS-CoV-2
coronavirus,
which
emerged
in
late
2019,
is
a
highly
variable
causative
agent
of
COVID-19,
contagious
respiratory
disease
with
potentially
severe
complications.
Vaccination
considered
the
most
effective
measure
to
prevent
spread
and
complications
this
infection.
Spike
(S)
protein-based
vaccines
were
very
successful
preventing
COVID-19
caused
by
ancestral
strain;
however,
their
efficacy
was
significantly
reduced
when
coronavirus
variants
antigenically
different
from
original
strain
circulation.
This
due
high
variability
major
viral
antigen
escape
immunity
infection
or
vaccination
spike-targeting
vaccines.
nucleocapsid
protein
(N)
much
more
conserved
than
spike
has
therefore
attracted
attention
scientists
as
promising
target
for
broad-spectrum
vaccine
development.
Here,
we
summarized
current
data
on
various
N-based
that
have
been
tested
animal
challenge
models
clinical
trials.
Despite
conservatism
N
protein,
mutations
gradually
occurring
sequence
can
affect
its
protective
properties.
During
three
years
pandemic,
at
least
12
arisen
sequence,
affecting
40
known
immunogenic
T-cell
epitopes,
so
antigenicity
recent
may
be
altered.
fact
should
taken
into
account
limitation
development
cross-reactive
based
N-protein.
Journal of Clinical Investigation,
Год журнала:
2022,
Номер
132(23)
Опубликована: Окт. 11, 2022
The
severe
acute
respiratory
syndrome
coronavirus
2
(SARS-CoV-2)
spike
protein
is
the
main
antigen
in
all
approved
COVID-19
vaccines
and
also
only
target
for
monoclonal
antibody
(mAb)
therapies.
Immune
responses
to
other
viral
antigens
are
generated
after
SARS-CoV-2
infection,
but
their
contribution
antiviral
response
remains
unclear.
Here,
we
interrogated
whether
nucleocapsid-specific
antibodies
can
improve
protection
against
SARS-CoV-2.
We
first
immunized
mice
with
a
nucleocapsid-based
vaccine
then
transferred
sera
from
these
into
naive
mice,
followed
by
challenge
show
that
received
or
mAb
exhibited
enhanced
control
of
Nucleocapsid-specific
elicited
NK-mediated,
antibody-dependent
cellular
cytotoxicity
(ADCC)
infected
cells.
To
our
knowledge,
findings
provide
demonstration
literature
specific
nucleocapsid
clearance,
providing
rationale
clinical
evaluation
therapies
treat
COVID-19.
Cell Reports,
Год журнала:
2023,
Номер
42(3), С. 112167 - 112167
Опубликована: Фев. 15, 2023
mRNA
vaccines
are
effective
in
preventing
severe
COVID-19,
but
breakthrough
infections,
emerging
variants,
and
waning
immunity
warrant
the
use
of
boosters.
Although
boosters
being
implemented,
extent
to
which
pre-existing
influences
efficacy
remains
unclear.
In
a
cohort
individuals
primed
with
mRNA-1273
or
BNT162b2
vaccines,
we
report
that
lower
antibody
levels
before
boost
associated
higher
fold-increase
after
boost,
suggesting
modulates
immunogenicity
vaccines.
Our
studies
mice
show
antibodies
accelerate
clearance
vaccine
antigen
via
Fc-dependent
mechanisms,
limiting
amount
available
prime
B
cell
responses
These
data
demonstrate
"tug
war"
between
de
novo
following
vaccination,
they
suggest
transient
downmodulation
effector
function
may
improve
Annual Review of Medicine,
Год журнала:
2023,
Номер
75(1), С. 145 - 157
Опубликована: Сен. 19, 2023
The
treatment
for
COVID-19
has
evolved
rapidly
since
the
start
of
pandemic
and
now
consists
mainly
antiviral
immunomodulatory
agents.
Antivirals,
such
as
remdesivir
nirmatrelvir-ritonavir,
have
proved
to
be
most
useful
earlier
in
illness
(e.g.,
outpatient
therapy)
less
severe
disease.
Immunomodulatory
therapies,
dexamethasone
interleukin-6
or
Janus
kinase
inhibitors,
are
disease
critical
illness.
role
anti-SARS-CoV-2
monoclonal
antibodies
diminished
because
emergence
viral
variants
that
not
anticipated
susceptible
these
treatments,
there
still
is
a
consensus
on
use
convalescent
plasma.
been
associated
with
increased
rates
venous
thromboembolism,
but
antithrombotic
therapy
limited.
Multiple
investigational
agents
continue
studied,
which
will
alter
current
paradigms
new
data
released.
PLoS Pathogens,
Год журнала:
2023,
Номер
19(10), С. e1011670 - e1011670
Опубликована: Окт. 5, 2023
Antibodies
that
can
bind
to
viruses
but
are
unable
block
infection
in
cell
culture
known
as
"nonneutralizing
antibodies."
Such
antibodies
nearly
universally
elicited
following
viral
and
have
been
characterized
infections
such
influenza,
rotavirus,
cytomegalovirus,
HIV,
SARS-CoV-2.
It
has
widely
assumed
these
nonneutralizing
do
not
function
a
protective
way
vivo
therefore
desirable
targets
of
antiviral
interventions;
however,
increasing
evidence
now
shows
this
be
true.
Several
virus-specific
antibody
responses
correlated
with
protection
human
studies
also
shown
significantly
reduce
virus
replication
animal
models.
The
mechanisms
by
which
many
is
only
coming
light.
While
cannot
prevent
entering
their
host
cell,
work
the
extracellular
space
recruit
effector
proteins
or
cells
destroy
antibody-virus
complex.
Other
exert
effects
inside
cells,
either
blocking
life
cycle
directly
recruiting
intracellular
Fc
receptor
TRIM21.
In
review,
we
will
discuss
multitude
ways
against
range
infections.
Nature Communications,
Год журнала:
2023,
Номер
14(1)
Опубликована: Июнь 7, 2023
Abstract
The
nucleocapsid
protein
(N)
of
SARS-CoV-2
plays
a
pivotal
role
during
the
viral
life
cycle.
It
is
involved
in
RNA
transcription
and
accounts
for
packaging
large
genome
into
virus
particles.
N
manages
enigmatic
balance
bulk
RNA-coating
versus
precise
RNA-binding
to
designated
cis-regulatory
elements.
Numerous
studies
report
involvement
its
disordered
segments
non-selective
RNA-recognition,
but
how
organizes
inevitable
recognition
specific
motifs
remains
unanswered.
We
here
use
NMR
spectroscopy
systematically
analyze
interactions
N’s
N-terminal
domain
(NTD)
with
individual
cis
elements
clustering
regulatory
5’-genomic
end.
Supported
by
broad
solution-based
biophysical
data,
we
unravel
NTD
preferences
natural
context.
show
that
domain’s
flexible
regions
read
intrinsic
signature
preferred
selective
stable
complex
formation
within
pool
available
motifs.
Frontiers in Immunology,
Год журнала:
2023,
Номер
14
Опубликована: Июнь 19, 2023
Spike-based
COVID-19
vaccines
induce
potent
neutralizing
antibodies
but
their
efficacy
against
SARS-CoV-2
variants
decreases.
OVX033
is
a
recombinant
protein
composed
of
the
full-length
nucleocapsid
(N)
genetically
fused
to
oligoDOM
®
,
self-assembling
domain
which
improves
antigen
immunogenicity.
including
N
as
an
antigenic
target
proposed
new
vaccine
candidate
providing
broad-spectrum
protection
sarbecoviruses.
demonstrated
its
ability
trigger
cross-reactive
T
cell
responses
and
cross-protection
three
(B.1
Europe,
Delta
B.1.617.2,
Omicron
B.1.1.529)
in
hamster
challenge
model,
evidenced
by
lower
weight
loss,
lung
viral
loads,
reduced
histopathological
lesions.
Emerging Microbes & Infections,
Год журнала:
2022,
Номер
12(1)
Опубликована: Дек. 30, 2022
ABSTRACTThe
coronavirus
disease
2019
(COVID-19)
has
caused
enormous
health
risks
and
global
economic
disruption.
This
is
by
the
severe
acute
respiratory
syndrome
2
(SARS-CoV-2).
The
SARS-CoV-2
nucleocapsid
protein
a
structural
involved
in
viral
replication
assembly.
There
accumulating
evidence
indicating
that
multi-functional,
playing
key
role
pathogenesis
of
COVID-19
antiviral
immunity
against
SARS-CoV-2.
Here,
we
summarize
its
potential
application
prevention
COVID-19,
which
based
on
inflammation,
cell
death,
innate
immunity,
adaptive
immunity.
International Journal of Molecular Sciences,
Год журнала:
2023,
Номер
24(6), С. 5352 - 5352
Опубликована: Март 10, 2023
More
than
three
years
ago,
the
Severe
Acute
Respiratory
Syndrome
Coronavirus
2
(SARS-CoV-2)
caused
unforeseen
COVID-19
pandemic
with
millions
of
deaths.
In
meantime,
SARS-CoV-2
has
become
endemic
and
is
now
part
repertoire
viruses
causing
seasonal
severe
respiratory
infections.
Due
to
several
factors,
among
them
development
immunity
through
natural
infection,
vaccination
current
dominance
seemingly
less
pathogenic
strains
belonging
omicron
lineage,
situation
stabilized.
However,
challenges
remain
possible
new
occurrence
highly
variants
remains
a
threat.
Here
we
review
development,
features
importance
assays
measuring
neutralizing
antibodies
(NAbs).
particular
focus
on
in
vitro
infection
molecular
interaction
studying
binding
receptor
domain
(RBD)
its
cognate
cellular
ACE2.
These
assays,
but
not
measurement
SARS-CoV-2-specific
per
se,
can
inform
us
whether
produced
by
convalescent
or
vaccinated
subjects
may
protect
against
thus
have
potential
predict
risk
becoming
newly
infected.
This
information
extremely
important
given
fact
that
considerable
number
subjects,
vulnerable
persons,
respond
poorly
production
antibodies.
Furthermore,
these
allow
determine
evaluate
virus-neutralizing
capacity
induced
vaccines
administration
plasma-,
immunoglobulin
preparations,
monoclonal
antibodies,
ACE2
synthetic
compounds
be
used
for
therapy
assist
preclinical
evaluation
vaccines.
Both
types
relatively
quickly
adapted
emerging
virus
about
magnitude
cross-neutralization,
which
even
estimate
infected
appearing
variants.
Given
paramount
discuss
their
specific
features,
advantages
disadvantages,
technical
aspects
yet
fully
resolved
issues,
such
as
cut-off
levels
predicting
degree
vivo
protection.
Frontiers in Microbiology,
Год журнала:
2023,
Номер
14
Опубликована: Авг. 14, 2023
Despite
many
countries
rapidly
revising
their
strategies
to
prevent
contagions,
the
number
of
people
infected
with
Severe
acute
respiratory
syndrome
coronavirus
2
(SARS-CoV-2)
continues
surge.
The
emergent
variants
that
can
evade
immune
response
significantly
affect
effectiveness
mainstream
vaccines
and
diagnostic
products
based
on
original
spike
protein.
Therefore,
it
is
essential
focus
highly
conserved
nature
nucleocapsid
protein
as
a
potential
target
in
field
diagnostics.
In
this
regard,
our
review
initially
discusses
structure,
function,
mechanism
action
N
Based
discussion,
we
summarize
relevant
research
in-depth
development
application
methods
protein,
such
serology
nucleic
acid
detection.
Such
valuable
information
aid
designing
more
efficient
vaccine
tools
could
help
end
SARS-CoV-2
pandemic.
Genetic
diversity
is
a
hallmark
of
RNA
viruses
and
the
basis
for
their
evolutionary
success.
Taking
advantage
uniquely
large
genomic
database
SARS-CoV-2,
we
examine
impact
mutations
across
spectrum
viable
amino
acid
sequences
on
biophysical
phenotypes
highly
expressed
multifunctional
nucleocapsid
protein.
We
find
variation
in
physicochemical
parameters
its
extended
intrinsically
disordered
regions
(IDRs)
sufficient
to
allow
local
plasticity,
but
also
observe
functional
constraints
that
similarly
occur
related
coronaviruses.
In
experiments
with
several
N-protein
species
carrying
associated
major
variants,
point
IDRs
can
have
nonlocal
modulate
thermodynamic
stability,
secondary
structure,
protein
oligomeric
state,
particle
formation,
liquid-liquid
phase
separation.
Omicron
variant,
distant
different
compensatory
effects
shifting
delicate
balance
interactions
controlling
assembly
properties,
include
creation
new
protein-protein
interaction
interface
N-terminal
IDR
through
defining
P13L
mutation.
A
picture
emerges
where
genetic
accompanied
by
significant
characteristics
species,
particular
IDRs.