Uirusu,
Journal Year:
2023,
Volume and Issue:
73(2), P. 153 - 162
Published: Jan. 1, 2023
Severe
acute
respiratory
syndrome
(SARS)
corona
virus
2
(SARS-CoV-2)
is
a
novel
coronavirus
that
infects
humans
and
causes
symptoms,
resulting
in
global
pandemic
since
its
appearance
2019.
Neutralizing
antibody
production
an
important
immune
response
following
SARS-CoV-2
infection,
great
deal
of
research
has
been
performed
regarding
the
against
infection.
However,
constantly
changing
multiple
amino
acid
reconstitutions
accumulated
spike
protein
enabled
viruses
to
escape
from
responses,
especially
neutralizing
antibodies.
In
this
review,
responses
emergence
variants,
development
broadly
antibodies
will
be
introduced.
Expert Opinion on Biological Therapy,
Journal Year:
2024,
Volume and Issue:
24(8), P. 787 - 797
Published: Aug. 1, 2024
Monoclonal
antibody
(mAb)
therapies
proved
safe
and
effective
in
preventing
progression
of
COVID-19
to
hospitalization,
but
most
were
eventually
defeated
by
continued
viral
evolution.
mAb
combinations
those
mAbs
that
deliberatively
selected
target
conserved
regions
the
SARS-CoV-2
spike
protein
more
resilient
escape
variants
as
evident
longer
clinical
useful
lives.
ACS Omega,
Journal Year:
2024,
Volume and Issue:
9(4), P. 4684 - 4694
Published: Jan. 18, 2024
This
study
investigated
the
allosteric
action
within
receptor-binding
domain
(RBD)
of
SARS-CoV-2
spike
protein
caused
by
class
3
monoclonal
antibody
(mAb)
binding.
As
emergence
variants
has
raised
concerns
about
effectiveness
treatments
antibodies,
targeting
highly
conserved
epitopes
become
an
alternative
strategy
design.
Simulations
explicitly
solvated
RBD
BA.2.75
omicron
subvariants
were
carried
out
both
in
presence
and
absence
bebtelovimab,
as
a
model
example
antibodies
against
protein.
The
comparative
analysis
showed
that
bebtelovimab's
binding
on
two
α
helices
at
epitope
region
disrupted
nearby
interaction
network,
which
triggered
denser
network
formation
opposite
side
motif
(RBM)
resulted
"close"
conformation
could
prevent
ACE2
A
better
understanding
this
lead
to
development
mAbs
for
further
concern.
In
terms
computational
techniques,
communicability
matrix
serve
tool
visualize
effects
allostery,
pairs
amino
acids
or
secondary
structures
with
high
pinpoint
possible
sites
transfer
signal.
Additionally,
gain/loss
help
elucidate
consequences
actions,
be
employed
along
other
allostery
quantification
techniques
some
previous
studies.
PLoS Pathogens,
Journal Year:
2024,
Volume and Issue:
20(6), P. e1012246 - e1012246
Published: June 10, 2024
Antibody-mediated
immunity
plays
a
key
role
in
protection
against
SARS-CoV-2.
We
characterized
B-cell-derived
anti-SARS-CoV-2
RBD
antibody
repertoires
from
vaccinated
and
infected
individuals
elucidate
the
mechanism
of
action
broadly
neutralizing
antibodies
dissect
at
epitope
level.
The
breadth
clonality
anti-RBD
B
cell
response
varies
among
individuals.
majority
clones
lose
or
exhibit
reduced
activities
Beta,
Delta,
Omicron
variants.
Nevertheless,
portion
that
develops
after
primary
series
booster
dose
COVID-19
vaccination
broad
neutralization
emerging
BA.2,
BA.4,
BA.5,
BQ.1.1,
XBB.1.5
XBB.1.16
These
share
genetic
features
including
conserved
usage
IGHV3-53
3–9
genes
recognize
three
clustered
epitopes
RBD,
partially
overlap
classically
defined
set
identified
early
pandemic.
Fab-RBD
crystal
Fab-Spike
complex
structures
corroborate
grouping
reveal
detailed
binding
mode
antibodies.
Structure-guided
mutagenesis
improves
potency
with
variants
via
single
amino-substitution.
Together,
these
results
provide
an
immunological
basis
for
partial
severe
by
ancestral
strain-based
vaccine
indicate
guidance
next
generation
monoclonal
development
design.
bioRxiv (Cold Spring Harbor Laboratory),
Journal Year:
2023,
Volume and Issue:
unknown
Published: Oct. 11, 2023
Abstract
Understanding
the
molecular
properties
of
SARS-CoV-2
is
crucial
to
tackle
future
outbreaks.
Current
knowledge
trimeric
spike
protein
relies
on
truncated
recombinant
proteins
and
inactivated
full-length
forms,
which
may
suffer
from
overstabilization.
Here,
we
apply
cryo-electron
tomography
(cryo-ET)
at
a
Biosafety
level
3
facility
study
virus
structure
in
its
native,
active
state.
The
particles
show
variable
shapes
with
diffusible
spikes,
majority
typical
prefusion
conformations.
Notably,
also
identified
unprecedented,
atypical
open-trimer
states,
revealing
hidden
flexibility.
sub-tomogram
averaged
suggests
loosely
packed
trimer.
observed
dynamics
uncover
conserved
cryptic
regions
that
can
be
targeted
for
broadly
effective
vaccines.
Structural
analysis
viruses
will
have
implications
understanding
overlooked
fusion
mechanism
vaccine,
antibody/drug
design.
(124
words)
One-Sentence
Summary
BSL3
microscopy
uncovered
significant
flexibility
viruses,
facilitate
design
vaccines
drugs.
Microbial Cell Factories,
Journal Year:
2024,
Volume and Issue:
23(1)
Published: Feb. 6, 2024
Abstract
Background
Developing
effective
vaccines
against
SARS-CoV-2
that
consider
manufacturing
limitations,
equitable
access,
and
acceptance
is
necessary
for
developing
platforms
to
produce
antigens
can
be
efficiently
presented
generating
neutralizing
antibodies
as
a
model
new
vaccines.
Results
This
work
presents
the
development
of
an
applicable
technology
through
oral
administration
RBD
antigen
fused
with
peptide
improve
its
antigenic
presentation.
We
focused
on
production
recombinant
receptor
binding
domain
(RBD)
produced
in
E.
coli
modified
addition
amino
acids
extension
designed
The
was
carried
out
shake
flask
bioreactor
cultures,
obtaining
around
200
mg/L
antigen.
peptide-fused
peptide-free
proteins
were
characterized
compared
using
SDS-PAGE
gel,
high-performance
chromatography,
circular
dichroism.
formulated
oil-in-water
emulsion
mice
immunization.
RBD,
induced
robust
IgG
mice,
capable
recognizing
Enzyme-linked
immunosorbent
assays.
In
addition,
generated
sera
dosed
mice.
formulation
showed
no
reactive
episodes
changes
temperature
or
vomiting.
Conclusions
Our
study
demonstrated
effectiveness
added
immunostimulation
by
administration.
Graphical
Problems of Particularly Dangerous Infections,
Journal Year:
2024,
Volume and Issue:
3, P. 111 - 117
Published: Oct. 1, 2024
The
aim
of
the
work
was
to
evaluate
ability
monoclonal
antibodies
inhibit
interaction
receptor
binding
domain
(RBD)
in
S
protein
SARS-CoV-2
virus
variants,
Wuhan-Hu-1
and
BQ
1.1,
with
angiotensin-converting
2
(ACE2).
Materials
methods.
In
this
study,
recombinant
RBDs
1.1
variants
were
used
as
antigens.
For
mouse
antibody
(mMCA)
production,
hybridomas
cultured
vivo
BALB/c
mice.
mMCAs
isolated
from
ascitic
fluid
by
ammonium
sulfate
treatment
followed
purification
through
column
affinity
chromatography
Protein
G
Sepharose
sorbent.
specific
activity
assessed
immunoblot
RBD
variant.
To
identify
most
promising
mMCA,
neutralizing
mMCA
evaluated
enzyme-linked
immunosorbent
assay
(ELISA)
via
immobilizing
on
surface
a
microplate
using
ACE2
form
horseradish
peroxidase
conjugate.
Recombinant
antigens
produced
ExpiCHO-S
cell
line
(Gibco,
USA).
Results
discussion.
Three
have
been
described
result
study:
5C3,
3F11,
1E6.
All
belong
immunoglobulins
subclass
specifically
interact
virus.
effective
inhibition
between
strain
observed
for
murine
MCA
3F11
(65
%),
while
inhibited
5C3
(91
%).
identified
characteristics
allow
considering
potential
candidates
development
antibody-based
therapeutics,
thus
expanding
possibilities
therapy
infection.
Vaccines,
Journal Year:
2023,
Volume and Issue:
11(9), P. 1451 - 1451
Published: Sept. 3, 2023
The
ideal
vaccine
against
viral
infections
should
elicit
antibody
responses
that
protect
divergent
strains.
Designing
broadly
protective
vaccines
SARS-CoV-2
and
other
viruses
requires
insight
into
the
specific
targets
of
cross-protective
antibodies
on
surface
protein(s).
However,
unlike
therapeutic
monoclonal
antibodies,
B-cell
epitopes
vaccine-induced
polyclonal
remain
poorly
defined.
Here
we
show
that,
through
combination
neutralizing
functional
with
epitope
mapping,
it
is
possible
to
identify
unique
associated
neutralization
breadth.
profiles
index-strain-vaccinated
rabbits
demonstrated
a
low,
intermediate,
or
high
efficiency
different
variants
concern
(VOCs)
were
distinctly
different.
Animals
an
intermediate
cross-neutralization
VOCs
targeted
fewer
antigenic
sites
spike
protein
one
particular
epitope,
subdomain
1
(SD1),
situated
outside
receptor
binding
domain
(RBD).
Our
results
indicate
response
additional
focus
non-RBD
could
be
effective
for
broad
protection
variants.
We
anticipate
approach
taken
in
this
study
can
applied
identifying
future
confer
cross-neutralizing
responses,
our
findings
will
inform
rational
design
SARS-CoV-2.
bioRxiv (Cold Spring Harbor Laboratory),
Journal Year:
2023,
Volume and Issue:
unknown
Published: July 18, 2023
Abstract
The
rapid
emergence
of
SARS-CoV-2
variants
concern
(VOCs)
calls
for
efforts
to
study
broadly
neutralizing
antibodies
elicited
by
infection
or
vaccination
so
as
inform
the
development
vaccines
and
antibody
therapeutics
with
broad
protection.
Here,
we
identified
two
convalescents
breakthrough
relatively
high
titers
against
all
tested
viruses
including
BQ
XBB
lineages.
Among
50
spike-specific
monoclonal
(mAbs)
cloned
from
their
B
cells,
top
6
mAbs
(KXD01-06)
belong
previously
defined
IGHV3-53/3-66
public
antibodies.
Although
most
in
this
class
are
dramatically
escaped
VOCs,
KXD01-06
exhibit
capacity
IC50s
KXD01
ranging
0.011∼0.059μg/ml.
Deep
mutational
scanning
reveals
that
target
highly
conserved
sites
on
RBD
D420,
Y421,
L455,
F456,
A475
N487.
Genetic
functional
analysis
further
indicates
extent
somatic
hypermutation
is
critical
breadth
Overall,
discovered
characterized
potent
activity
SARS-CoV-2,
which
provides
rationale
novel
based
Uirusu,
Journal Year:
2023,
Volume and Issue:
73(2), P. 153 - 162
Published: Jan. 1, 2023
Severe
acute
respiratory
syndrome
(SARS)
corona
virus
2
(SARS-CoV-2)
is
a
novel
coronavirus
that
infects
humans
and
causes
symptoms,
resulting
in
global
pandemic
since
its
appearance
2019.
Neutralizing
antibody
production
an
important
immune
response
following
SARS-CoV-2
infection,
great
deal
of
research
has
been
performed
regarding
the
against
infection.
However,
constantly
changing
multiple
amino
acid
reconstitutions
accumulated
spike
protein
enabled
viruses
to
escape
from
responses,
especially
neutralizing
antibodies.
In
this
review,
responses
emergence
variants,
development
broadly
antibodies
will
be
introduced.
