Cell Reports,
Год журнала:
2024,
Номер
43(8), С. 114520 - 114520
Опубликована: Июль 17, 2024
Highlights•SLip,
FLiRT,
and
KP.2
are
poorly
neutralized
by
bivalent-vaccinated
sera•XBB.1.5-vaccinated
hamster
JN.1
patient
sera
SLip,
KP.2•S
mutations
R346T,
L455S,
F456L
alter
ACE2
binding
neutralization
epitopes•SLip,
spikes
exhibit
less
fusion
processing
relative
to
JN.1SummaryWe
investigate
JN.1-derived
subvariants
for
antibodies
in
vaccinated
individuals,
severe
acute
respiratory
syndrome
coronavirus
2
(SARS-CoV-2)-infected
patients,
or
class
III
monoclonal
antibody
S309.
Compared
JN.1,
KP.2,
especially
FLiRT
increased
resistance
BA.2.86/JN.1-wave
convalescent
human
sera.
XBB.1.5
monovalent-vaccinated
robustly
neutralize
but
have
reduced
efficiency
SLip.
All
resistant
S309
show
decreased
infectivity,
cell-cell
fusion,
spike
JN.1.
Modeling
reveals
that
L455S
SLip
reduce
ACE2,
while
R346T
strengthens
it.
These
three
mutations,
alongside
D339H,
key
epitopes
spike,
likely
explaining
the
sensitivity
of
these
neutralization.
Our
findings
highlight
suggest
future
vaccine
formulations
should
consider
as
an
immunogen,
although
current
monovalent
could
still
offer
adequate
protection.Graphical
abstract
bioRxiv (Cold Spring Harbor Laboratory),
Год журнала:
2024,
Номер
unknown
Опубликована: Май 21, 2024
SARS-CoV-2
variants
derived
from
the
immune
evasive
JN.1
are
on
rise
worldwide.
Here,
we
investigated
JN.1-derived
subvariants
SLip,
FLiRT,
and
KP.2
for
their
ability
to
be
neutralized
by
antibodies
in
bivalent-vaccinated
human
sera,
XBB.1.5
monovalent-vaccinated
hamster
sera
people
infected
during
BA.2.86/JN.1
wave,
class
III
monoclonal
antibody
(Mab)
S309.
We
found
that
compared
parental
JN.1,
SLip
KP.2,
especially
exhibit
increased
resistance
COVID-19
BA.2.86/JN.1-wave
convalescent
sera.
Interestingly,
monovalent
vaccinated
robustly
FLiRT
but
had
reduced
efficiency
SLip.
These
were
resistant
neutralization
Mab
In
addition,
aspects
of
spike
protein
biology
including
infectivity,
cell-cell
fusion
processing,
these
subvariants,
a
decreased
infectivity
membrane
relative
correlating
with
processing.
Homology
modeling
revealed
L455S
F456L
mutations
local
hydrophobicity
hence
its
binding
ACE2.
contrast,
additional
R346T
mutation
strengthened
conformational
support
receptor-binding
motif,
thus
counteracting
effects
F456L.
three
mutations,
alongside
D339H,
which
is
present
all
sublineages,
alter
epitopes
targeted
therapeutic
Mabs,
I
S309,
explaining
sensitivity
Together,
our
findings
provide
insight
into
newly
emerged
suggest
future
vaccine
formulations
should
consider
as
immunogen,
although
current
could
still
offer
adequate
protection.
Signal Transduction and Targeted Therapy,
Год журнала:
2025,
Номер
10(1)
Опубликована: Янв. 27, 2025
Abstract
The
newly
emerged
variants
of
severe
acute
respiratory
syndrome
coronavirus-2
(SARS-CoV-2)
demonstrate
resistance
to
present
therapeutic
antibodies
as
well
the
capability
evade
vaccination-elicited
antibodies.
JN.1
sublineages
were
demonstrated
one
most
immune-evasive
variants,
showing
higher
neutralization
compared
XBB.1.5.
In
this
study,
serum
samples
collected
from
adult
participants
including
those
who
had
gone
through
BA.5/BF.7,
EG.5/HK.3
and
XBB/JN.1
infection
waves,
characterized
by
different
vaccination
histories.
We
evaluated
in
these
against
pseudoviruses
Omicron
lineages.
further
investigated
humoral
immune
response
recombinant
XBB
vaccines
estimated
sublineages,
KP.2
KP.3.
Our
results
showed
that
sera
previous
circulating
subvariant
breakthrough
infections
exhibited
low
GMTs
50%
all
tested
significantly
elevated
individuals
received
WSK-V102C
or
WSK-V102D
boosters.
Importantly,
4
months
after
a
booster
XBB.1.5,
JN.1,
JN.1.13,
KP.3
3479,
1684,
1397,
1247
1298,
with
9.86-,
9.79-,
8.73-,
8.66-
8.16-fold
increase
without
booster,
respectively,
indicating
boosting
XBB.1.5
subunit
still
induced
strong
antibody
responses
sublineages.
However,
KP.3,
revealed
more
than
2-fold
decreases
neutralizing
titers
suggesting
enhanced
evasion
necessity
boosters
based
on
bioRxiv (Cold Spring Harbor Laboratory),
Год журнала:
2024,
Номер
unknown
Опубликована: Сен. 5, 2024
SUMMARY
During
the
summer
of
2024,
COVID-19
cases
surged
globally,
driven
by
variants
derived
from
JN.1
subvariants
SARS-CoV-2
that
feature
new
mutations,
particularly
in
N-terminal
domain
(NTD)
spike
protein.
In
this
study,
we
report
on
neutralizing
antibody
(nAb)
escape,
infectivity,
fusion,
and
stability
these
subvariants—LB.1,
KP.2.3,
KP.3,
KP.3.1.1.
Our
findings
demonstrate
all
are
highly
evasive
nAbs
elicited
bivalent
mRNA
vaccine,
XBB.1.5
monovalent
mumps
virus-based
or
infections
during
BA.2.86/JN.1
wave.
This
reduction
nAb
titers
is
primarily
a
single
serine
deletion
(DelS31)
NTD
spike,
leading
to
distinct
antigenic
profile
compared
parental
other
variants.
We
also
found
DelS31
mutation
decreases
pseudovirus
infectivity
CaLu-3
cells,
which
correlates
with
impaired
cell-cell
fusion.
Additionally,
protein
appears
more
conformationally
stable,
as
indicated
reduced
S1
shedding
both
without
stimulation
soluble
ACE2,
increased
resistance
elevated
temperatures.
Molecular
modeling
suggests
induces
conformational
change
stabilizes
strengthens
NTD-Receptor-Binding
Domain
(RBD)
interaction,
thus
favoring
down
conformation
RBD
reducing
accessibility
ACE2
receptor
certain
nAbs.
introduces
an
N-linked
glycan
modification
at
N30,
shields
underlying
region
recognition.
data
highlight
critical
role
mutations
for
evasion,
stability,
viral
suggest
consideration
updating
vaccines
antigens
containing
DelS31.
Nature Communications,
Год журнала:
2024,
Номер
15(1)
Опубликована: Окт. 9, 2024
SARS-CoV-2
JN.1
with
an
additional
L455S
mutation
on
spike
when
compared
its
parental
variant
BA.2.86
has
outcompeted
all
earlier
variants
to
become
the
dominant
circulating
variant.
Recent
studies
investigated
immune
resistance
of
but
factors
are
speculated
contribute
global
dominance,
which
remain
elusive
until
today.
Here,
we
find
that
a
higher
infectivity
than
in
differentiated
primary
human
nasal
epithelial
cells
(hNECs).
Mechanistically,
demonstrate
gained
over
associates
increased
entry
efficiency
conferred
by
and
better
cleavage
hNECs.
Structurally,
S455
altered
mode
binding
protein
ACE2
at
The
JN.1
variant
of
COVID-19
has
emerged
as
the
dominant
strain
worldwide
since
end
2023.
As
a
subclade
BA.2.86
variant,
harbors
unique
combination
mutations
inherited
from
lineage,
notably
featuring
novel
L455S
mutation
within
its
receptor-binding
motif.
This
been
linked
to
increased
transmissibility
and
enhanced
immune
evasion
capabilities.
During
rise
JN.1,
evidence
resistance
various
monoclonal
antibodies
reduced
cross-neutralization
effects
XBB.1.5
vaccine
have
observed.
Although
public
health
threat
posed
by
appears
relatively
low,
concerns
persist
regarding
evolutionary
trajectory
under
pressure.
review
provides
comprehensive
overview
evolving
highlighting
need
for
continuous
monitoring
investigation
new
variants
that
could
lead
widespread
infection.
It
assesses
efficacy
current
vaccines
therapeutics
against
emerging
variants,
particularly
focusing
on
immunocompromised
populations.
Additionally,
this
summarizes
potential
advancements
clinical
treatments
COVID-19,
offering
insights
optimize
prevention
treatment
strategies.
thoroughly
evaluates
variant's
impact
implications
future
therapeutic
development,
contributing
ongoing
efforts
mitigate
risk
virus
transmission
disease
severity.
ABSTRACT
During
the
summer
of
2024,
coronavirus
disease
2019
(COVID-19)
cases
surged
globally,
driven
by
variants
derived
from
JN.1
subvariants
severe
acute
respiratory
syndrome
2
that
feature
new
mutations,
particularly
in
N-terminal
domain
(NTD)
spike
protein.
In
this
study,
we
report
on
neutralizing
antibody
(nAb)
escape,
infectivity,
fusion,
and
stability
these
subvariants—LB.1,
KP.2.3,
KP.3,
KP.3.1.1.
Our
findings
demonstrate
all
are
highly
evasive
nAbs
elicited
bivalent
mRNA
vaccine,
XBB.1.5
monovalent
mumps
virus-based
or
infections
during
BA.2.86/JN.1
wave.
This
reduction
nAb
titers
is
primarily
a
single
serine
deletion
(DelS31)
NTD
spike,
leading
to
distinct
antigenic
profile
compared
parental
other
variants.
We
also
found
DelS31
mutation
decreases
pseudovirus
infectivity
CaLu-3
cells,
which
correlates
with
impaired
cell-cell
fusion.
Additionally,
protein
appears
more
conformationally
stable,
as
indicated
reduced
S1
shedding
both
without
stimulation
soluble
ACE2
increased
resistance
elevated
temperatures.
Molecular
modeling
suggests
enhances
NTD-receptor-binding
(RBD)
interaction,
favoring
RBD
down
conformation
reducing
accessibility
specific
nAbs.
Moreover,
introduces
an
N-linked
glycan
at
N30,
shielding
recognition.
These
underscore
role
mutations
immune
evasion,
stability,
viral
highlighting
need
consider
DelS31-containing
antigens
updated
COVID-19
vaccines.
IMPORTANCE
The
emergence
novel
continues
pose
challenges
for
global
public
health,
context
evasion
stability.
study
identifies
key
mutation,
DelS31,
JN.1-derived
escape
while
stabilizes
conformation,
limits
shedding,
increases
thermal
resistance,
possibly
contribute
prolonged
persistence.
Structural
analyses
reveal
interactions
introducing
shielding,
thus
decreasing
accessibility.
emphasize
critical
shaping
evolution
underscoring
urgent
vaccines
account
adaptive
changes.
