Vaccines,
Journal Year:
2023,
Volume and Issue:
11(4), P. 875 - 875
Published: April 20, 2023
Immunological
memory
is
the
key
source
of
protective
immunity
against
pathogens.
At
current
stage
COVID-19
pandemic,
heterologous
combinations
exposure
to
viral
antigens
during
infection
and/or
vaccination
shape
a
distinctive
immunological
memory.
Immune
imprinting,
downside
memory,
might
limit
generation
de
novo
immune
response
variant
or
next-generation
vaccines.
Here,
we
review
mechanistic
basis
imprinting
by
focusing
on
B
cell
immunobiology
and
discuss
extent
which
harmful,
as
well
its
effect
SARS-CoV-2
vaccination.
ACS Central Science,
Journal Year:
2023,
Volume and Issue:
9(2), P. 252 - 265
Published: Feb. 8, 2023
The
spike
protein
of
SARS-CoV-2
has
been
a
promising
target
for
developing
vaccines
and
therapeutics
due
to
its
crucial
role
in
the
viral
entry
process.
Previously
reported
cryogenic
electron
microscopy
(cryo-EM)
structures
have
revealed
that
free
fatty
acids
(FFA)
bind
with
protein,
stabilizing
closed
conformation
reducing
interaction
host
cell
vitro.
Inspired
by
these,
we
utilized
structure-based
virtual
screening
approach
against
conserved
FFA-binding
pocket
identify
small
molecule
modulators
which
helped
us
six
hits
micromolar
binding
affinities.
Further
evaluation
their
commercially
available
synthesized
analogs
enabled
discover
series
compounds
better
affinities
solubilities.
Notably,
our
identified
exhibited
similar
proteins
prototypic
currently
circulating
Omicron
BA.4
variant.
Furthermore,
cryo-EM
structure
compound
SPC-14
bound
could
shift
conformational
equilibrium
toward
conformation,
is
human
ACE2
(hACE2)
inaccessible.
Our
targeting
serve
as
starting
point
future
development
broad-spectrum
COVID-19
intervention
treatments.
Journal of Chemical Information and Modeling,
Journal Year:
2023,
Volume and Issue:
63(16), P. 5272 - 5296
Published: Aug. 7, 2023
The
new
generation
of
SARS-CoV-2
Omicron
variants
displayed
a
significant
growth
advantage
and
increased
viral
fitness
by
acquiring
convergent
mutations,
suggesting
that
the
immune
pressure
can
promote
evolution
leading
to
sudden
acceleration
evolution.
In
current
study,
we
combined
structural
modeling,
microsecond
molecular
dynamics
simulations,
Markov
state
models
characterize
conformational
landscapes
identify
specific
dynamic
signatures
spike
complexes
with
host
receptor
ACE2
for
recently
emerged
highly
transmissible
XBB.1,
XBB.1.5,
BQ.1,
BQ.1.1
variants.
Microsecond
simulations
Markovian
modeling
provided
detailed
characterization
functional
states
revealed
thermodynamic
stabilization
XBB.1.5
subvariant,
which
be
contrasted
more
BQ.1
subvariants.
Despite
considerable
similarities,
mutations
induce
unique
distributions
states.
results
suggested
variant-specific
changes
mobility
in
interfacial
loops
receptor-binding
domain
protein
fine-tuned
through
crosstalk
between
could
provide
an
evolutionary
path
modulation
escape.
By
combining
atomistic
analysis
perturbation-based
approaches,
determined
important
complementary
roles
mutation
sites
as
effectors
receivers
allosteric
signaling
involved
plasticity
regulation
communications.
This
study
also
hidden
pockets
control
distribution
flexible
adaptable
regions.
Nature Communications,
Journal Year:
2023,
Volume and Issue:
14(1)
Published: Aug. 21, 2023
Abstract
Pronounced
immune
escape
by
the
SARS-CoV-2
Omicron
variant
has
resulted
in
many
individuals
possessing
hybrid
immunity,
generated
through
a
combination
of
vaccination
and
infection.
Concerns
have
been
raised
that
omicron
breakthrough
infections
triple-vaccinated
result
poor
induction
omicron-specific
prior
infection
is
associated
with
dampening.
Taking
broad
comprehensive
approach,
we
characterize
mucosal
blood
immunity
to
spike
non-spike
antigens
following
BA.1/BA.2
triple
mRNA-vaccinated
individuals,
without
We
find
most
increase
BA.1/BA.2/BA.5-specific
neutralizing
antibodies
infection,
but
confirm
magnitude
post-omicron
titres
are
higher
infection-naive.
In
contrast,
significant
increases
nasal
responses,
including
activity
against
BA.5
spike,
seen
regardless
history.
Spike-specific
T
cells
only
infection-naive
vaccinees;
however,
cell
responses
significantly
previously-infected,
who
display
maximally
induced
response
highly
cytotoxic
CD8+
phenotype
their
3
rd
mRNA
vaccine
dose.
Responses
status.
These
findings
suggest
characterized
enhancement
can
help
protect
future
variants.
Vaccines,
Journal Year:
2023,
Volume and Issue:
11(4), P. 875 - 875
Published: April 20, 2023
Immunological
memory
is
the
key
source
of
protective
immunity
against
pathogens.
At
current
stage
COVID-19
pandemic,
heterologous
combinations
exposure
to
viral
antigens
during
infection
and/or
vaccination
shape
a
distinctive
immunological
memory.
Immune
imprinting,
downside
memory,
might
limit
generation
de
novo
immune
response
variant
or
next-generation
vaccines.
Here,
we
review
mechanistic
basis
imprinting
by
focusing
on
B
cell
immunobiology
and
discuss
extent
which
harmful,
as
well
its
effect
SARS-CoV-2
vaccination.
