Long-Term Immune Consequences of Initial SARS-CoV-2 A.23.1 Exposure: A Longitudinal Study of Antibody Responses and Cross-Neutralization in a Ugandan Cohort
Vaccines,
Год журнала:
2025,
Номер
13(2), С. 143 - 143
Опубликована: Янв. 29, 2025
Background:
This
study
assessed
the
long-term
dynamics
of
neutralizing
antibodies
in
a
Ugandan
cohort
primarily
exposed
to
A.23.1
SARS-CoV-2
variant,
examining
how
this
shaped
immune
breadth
and
potency
against
diverse
strains
following
infection
prototype-based
vaccination.
Methods:
We
conducted
427-day
retrospective
analysis
41
participants
across
multiple
waves,
assessing
binding
antibody
responses
using
in-house
ELISA
pseudotyped
virus
neutralization
assays.
quantified
key
variants,
A.23.1,
D614G,
Delta,
BA.4,
capturing
evolving
immunity
pandemic.
Results:
Neutralizing
titers
remained
significantly
higher
than
those
highlighting
solid
memory
infection.
Consistently
lower
were
observed
for
BA.4
all
time
points,
aligning
with
its
strong
immune-evasion
capability.
Correlations
between
spike-directed
IgG
(S-IgG)
concentrations
stronger
no
correlation
BA.4.
ChAdOx1-S
vaccination
substantially
elevated
most
notably
essential
role
boosting
immunity,
even
individuals
initially
low
titers.
Conclusions:
Initial
exposure
variant
triggered
potent
responses,
shaping
during
subsequent
exposures.
These
findings
highlight
importance
accounting
early
viral
exposures
vaccine
development
public
health
planning.
The
distinctly
response
highlights
need
continuous
antigenic
monitoring
timely
updates
protection
emerging
variants.
Vaccination
remains
reinforcing
sustaining
Язык: Английский
Adaptive evolution of SARS-CoV-2 during a persistent infection for 521 days in an immunocompromised patient
npj Genomic Medicine,
Год журнала:
2025,
Номер
10(1)
Опубликована: Янв. 17, 2025
Immunocompromised
patients
struggle
to
adequately
clear
viral
infections,
offering
the
virus
opportunity
adapt
immune
system
in
host.
Here
we
present
a
case
study
of
patient
undergoing
allogeneic
hematopoietic
stem
cell
transplantation
with
521-day
follow-up
SARS-CoV-2
infection
BF.7.21
variant.
Virus
samples
from
five
time
points
were
submitted
whole
genome
sequencing.
Between
first
detection
and
its
clearance,
patient's
population
acquired
34
amino
acid
substitutions
8
deletions
coding
regions.
With
11
receptor
binding
domain
virus'
spike
protein,
15
times
more
abundant
than
expected
for
random
distribution
this
highly
functional
region.
Amongst
them
S:K417T,
S:N440S,
S:K444R,
S:V445A,
S:G446N,
S:L452Q,
S:N460K,
S:E484V
at
positions
that
are
notorious
their
resistance-mediating
effects.
The
substitution
patterns
found
indicate
ongoing
adaptive
evolution.
Язык: Английский
Role of N-linked glycosylation sites in human ACE2 in SARS-CoV-2 and hCoV-NL63 infection
Journal of Virology,
Год журнала:
2025,
Номер
unknown
Опубликована: Март 28, 2025
ABSTRACT
Angiotensin-converting
enzyme
2
(ACE2)
is
a
transmembrane
protein
known
for
its
physiological
role
in
the
renin-angiotensin
system
that
also
serves
as
receptor
entry
of
SARS-CoV-1,
SARS-CoV-2,
and
seasonal
human
coronavirus
NL63
(hCoV-NL63).
ACE2
contains
seven
N-linked
glycosylation
sites.
Molecular
simulation
binding
analyses
suggest
some
them
are
involved
interaction
with
Spike
(S)
proteins
hCoVs,
but
their
relevance
S-mediated
fusion
viral
poorly
investigated.
To
address
this,
we
determined
impact
all
sites
on
SARS-CoV-2
hCoV-NL63
infection
well
cell-to-cell
fusion.
We
found
mutant
expressed
localized
at
cell
surface,
albeit
lacks
glycans
decreased
levels.
On
average,
changes
T92I,
N322A,
N690A,
combined
mutation
increased
endocytic
VSVpp
mediated
by
early
HU-1
Omicron
BA.2,
BA.5,
XBB.1.5
S
proteins.
In
comparison,
only
lack
glycan
N322
enhanced
syncytia
formation
case
Changes
N90A,
N322A
strain
about
twofold
to
threefold
had
lesser
effects
genuine
variants.
Despite
reduced
surface
expression
ACE2,
elimination
usually
via
pathway
while
having
little
effect
presence
TMPRSS2.
Our
results
provide
insights
into
ability
(hACE2)
serve
receptors
infection.
IMPORTANCE
Several
coronaviruses
use
angiotensin-converting
primary
cells.
glycosylated
distinct
positions,
target
cells
incompletely
understood.
Here,
examined
individual
mutations
hACE2
Spike-mediated
VSV-pseudoparticle
new
information
highly
pathogenic
coronaviruses.
Язык: Английский
CRISPR-Cas9 genetic screens reveal regulation of TMPRSS2 by the Elongin BC-VHL complex
Scientific Reports,
Год журнала:
2025,
Номер
15(1)
Опубликована: Апрель 7, 2025
Abstract
The
TMPRSS2
cell
surface
protease
is
used
by
a
broad
range
of
respiratory
viruses
to
facilitate
entry
into
target
cells.
Together
with
ACE2,
represents
key
factor
for
SARS-CoV-2
infection,
as
mediates
cleavage
viral
spike
protein,
enabling
direct
fusion
the
envelope
host
membrane.
Since
start
COVID-19
pandemic,
has
gained
attention
therapeutic
inhibitors
which
would
inhibit
but
little
known
about
regulation,
particularly
in
types
physiologically
relevant
infection.
Here,
we
performed
an
unbiased
genome-wide
CRISPR-Cas9
library
screen,
together
targeted
at
epigenetic
modifiers
and
transcriptional
regulators,
identify
cellular
factors
that
modulate
expression
human
colon
epithelial
We
find
endogenous
regulated
Elongin
BC-VHL
complex
HIF
transcription
factors.
Depletion
B
or
treatment
cells
PHD
resulted
downregulation
inhibition
show
still
utilised
Omicron
variants
colonic
Our
study
enhances
our
understanding
regulation
Язык: Английский
Causes and Consequences of Coronavirus Spike Protein Variability
Опубликована: Янв. 3, 2024
Coronaviruses
are
a
large
family
of
diverse
enveloped
RNA
viruses
found
in
numerous
animal
species.
They
well-known
for
their
ability
to
cross
species
barriers
and
have
been
transmitted
from
bats
or
intermediate
hosts
humans
on
several
occasions.
Four
the
seven
human
coronaviruses
(hCoVs)
responsible
approximately
20%
common
colds
(hCoV-229E,
-NL63,
-OC43,
-HKU1).
Two
others
(SARS-CoV-1
MERS-CoV)
cause
severe
frequently
lethal
respiratory
syndromes
but
only
spread
very
limited
extents
populations.
In
contrast,
SARS-CoV-2,
while
exhibiting
pathogenicity,
has
profound
impact
public
health
due
its
enormous
spread.
this
review,
we
discuss
which
initial
features
SARS-CoV-2
Spike
protein
subsequent
adaptations
new
host
may
helped
pathogen
COVID-19
pandemic.
Our
focus
is
forces
driving
changes
consequences
virus
infectivity,
immune
evasion
resistance
preventive
therapeutic
agents.
addition,
significance
perspectives
broad-spectrum
therapeutics
vaccines.
Язык: Английский
Attenuated replication and damaging effects of SARS-CoV-2 Omicron variants in an intestinal epithelial barrier model
bioRxiv (Cold Spring Harbor Laboratory),
Год журнала:
2024,
Номер
unknown
Опубликована: Фев. 28, 2024
ABSTRACT
Many
COVID-19
patients
suffer
from
gastrointestinal
symptoms
and
impaired
intestinal
barrier
function
may
play
a
key
role
in
Long
COVID.
Despite
its
importance,
the
impact
of
SARS-CoV-2
on
epithelia
is
poorly
understood.
To
address
this,
we
established
an
model
integrating
epithelial
Caco-2
cells,
mucus-secreting
HT29
cells
human
Raji
cells.
This
gut
allows
efficient
differentiation
into
microfold-like
faithfully
mimics
function,
highly
permissive
to
infection.
Early
strains
Delta
variant
replicated
with
high
efficiency,
severely
disrupted
depleted
tight
junction
proteins,
such
as
claudin-1,
occludin
ZO-1.
In
comparison,
Omicron
subvariants
also
ZO-1
junctions
but
had
fewer
damaging
effects
mucosal
integrity
function.
Remdesivir
TMPRSS2
inhibitor
Camostat
prevented
replication
thus
damage,
while
Cathepsin
E64d
was
ineffective.
Our
results
support
that
disrupts
further
suggest
circulating
variants
are
less
than
earlier
viral
strains.
Язык: Английский
Causes and Consequences of Coronavirus Spike Protein Variability
Viruses,
Год журнала:
2024,
Номер
16(2), С. 177 - 177
Опубликована: Янв. 25, 2024
Coronaviruses
are
a
large
family
of
enveloped
RNA
viruses
found
in
numerous
animal
species.
They
well
known
for
their
ability
to
cross
species
barriers
and
have
been
transmitted
from
bats
or
intermediate
hosts
humans
on
several
occasions.
Four
the
seven
human
coronaviruses
(hCoVs)
responsible
approximately
20%
common
colds
(hCoV-229E,
-NL63,
-OC43,
-HKU1).
Two
others
(SARS-CoV-1
MERS-CoV)
cause
severe
frequently
lethal
respiratory
syndromes
but
only
spread
very
limited
extents
population.
In
contrast
most
recent
hCoV,
SARS-CoV-2,
while
exhibiting
pathogenicity,
has
profound
impact
public
health
due
its
enormous
spread.
this
review,
we
discuss
which
initial
features
SARS-CoV-2
Spike
protein
subsequent
adaptations
new
host
may
helped
pathogen
COVID-19
pandemic.
Our
focus
is
forces
driving
changes
consequences
virus
infectivity,
immune
evasion
resistance
preventive
therapeutic
agents.
addition,
briefly
address
significance
perspectives
broad-spectrum
therapeutics
vaccines.
Язык: Английский
Evaluating the Quality of Studies Assessing COVID-19 Vaccine Neutralizing Antibody Immunogenicity
Vaccines,
Год журнала:
2024,
Номер
12(11), С. 1238 - 1238
Опубликована: Окт. 30, 2024
COVID-19
vaccine-neutralizing
antibodies
provide
early
data
on
potential
vaccine
effectiveness,
but
their
usefulness
depends
study
reliability
and
reporting
quality.
Язык: Английский
Integration of Whole-Genome Sequencing with ddPCR Kit for Detection of Omicron Subvariants in Wastewater in the Upper Peninsula of Michigan
Applied Microbiology,
Год журнала:
2024,
Номер
4(4), С. 1453 - 1463
Опубликована: Окт. 13, 2024
This
study
explores
the
integration
of
genome
sequencing
and
digital
droplet
polymerase
chain
reaction
(ddPCR)-based
methods
for
tracking
diversity
COVID-19
variants
in
wastewater.
The
research
focuses
on
monitoring
various
Omicron
subvariants
during
a
period
significant
viral
evolution.
Genome
sequencing,
particularly
using
Oxford
Nanopore
Technology
(ONT),
provides
detailed
view
emerging
variants,
surpassing
limitations
PCR-based
detection
kits
that
rely
known
sequences.
Of
43
samples
analyzed,
39.5%
showed
matching
results
between
GT
Molecular
ddPCR
though
only
4%
were
exact
matches.
Some
mismatches
occurred
due
to
newer
like
XBB
BQ.1,
which
could
not
detect.
emphasized
kits,
variant
sequences,
while
real-time
data
offering
more
comprehensive
circulating
strains.
highlights
effectiveness
combining
these
methodologies
enhance
early
inform
public
health
strategies,
especially
regions
with
limited
clinical
capabilities.
Язык: Английский