Immunogenicity and safety of a live-attenuated SARS-CoV-2 vaccine candidate based on multiple attenuation mechanisms
Mie Suzuki-Okutani,
No information about this author
Shinya Okamura,
No information about this author
Tang Gis
No information about this author
et al.
eLife,
Journal Year:
2025,
Volume and Issue:
13
Published: Feb. 11, 2025
mRNA
vaccines
against
SARS-CoV-2
were
rapidly
developed
and
effective
during
the
pandemic.
However,
some
limitations
remain
to
be
resolved,
such
as
short-lived
induced
immune
response
certain
adverse
effects.
Therefore,
there
is
an
urgent
need
develop
new
that
address
these
issues.
While
live-attenuated
are
a
highly
modality,
they
pose
risk
of
effects,
including
virulence
reversion.
In
current
study,
we
constructed
vaccine
candidate,
BK2102,
combining
naturally
occurring
virulence-attenuating
mutations
in
NSP14
,
NSP1
spike,
ORF7-8
coding
regions.
Intranasal
inoculation
with
BK2102
humoral
cellular
responses
Syrian
hamsters
without
apparent
tissue
damage
lungs,
leading
protection
D614G
Omicron
BA.5
strains.
The
neutralizing
antibodies
by
persisted
for
up
364
days,
which
indicated
confer
long-term
infection.
Furthermore,
confirmed
safety
using
transgenic
(Tg)
mice
expressing
human
ACE2
(hACE2)
susceptible
SARS-CoV-2.
did
not
kill
Tg
mice,
even
when
virus
was
administered
at
dose
10
6
plaque-forming
units
(PFUs),
while
2
PFU
strain
or
attenuated
lacking
furin
cleavage
site
spike
sufficient
mice.
These
results
suggest
promising
live-vaccine
candidate
confers
significant
virulence.
Language: Английский
Immunogenicity and safety of a live-attenuated SARS-CoV-2 vaccine candidate based on multiple attenuation mechanisms
Mie Suzuki-Okutani,
No information about this author
Shinya Okamura,
No information about this author
Tanggis
No information about this author
et al.
Published: Jan. 6, 2025
mRNA
vaccines
against
SARS-CoV-2
were
rapidly
developed
and
effective
during
the
pandemic.
However,
some
limitations
remain
to
be
resolved,
such
as
short-lived
induced
immune
response
certain
adverse
effects.
Therefore,
there
is
an
urgent
need
develop
new
that
address
these
issues.
While
live-attenuated
are
a
highly
modality,
they
pose
risk
of
effects,
including
virulence
reversion.
In
current
study,
we
constructed
vaccine
candidate,
BK2102,
combining
naturally
occurring
virulence-attenuating
mutations
in
NSP14
,
NSP1
spike
ORF7-8
coding
regions.
Intranasal
inoculation
with
BK2102
humoral
cellular
responses
Syrian
hamsters
without
apparent
tissue
damage
lungs,
leading
protection
D614G
Omicron
BA.5
strains.
The
neutralizing
antibodies
by
persisted
for
up
364
days,
which
indicated
confer
long-term
infection.
Furthermore,
confirmed
safety
using
transgenic
(Tg)
mice
expressing
human
ACE2
(hACE2),
susceptible
SARS-CoV-2.
did
not
kill
Tg
mice,
even
when
virus
was
administered
at
dose
10
6
plaque-forming
units
(PFU),
while
2
PFU
strain
or
attenuated
lacking
furin
cleavage
site
(FCS)
sufficient
mice.
These
results
suggest
promising
live-vaccine
candidate
confers
significant
virulence.
Language: Английский
Amino acid substitutions in NSP6 and NSP13 of SARS-CoV-2 contribute to superior virus growth at low temperatures
Journal of Virology,
Journal Year:
2025,
Volume and Issue:
unknown
Published: Feb. 12, 2025
ABSTRACT
In
general,
severe
acute
respiratory
syndrome
coronavirus
2
(SARS-CoV-2)
replicates
well
at
37°C,
which
is
the
temperature
of
human
lower
tract,
but
it
poorly
30°C‒32°C,
upper
tract.
The
replication
efficiency
SARS-CoV-2
in
tract
may
directly
affect
its
transmissibility.
this
study,
an
XBB.1.5
isolate
showed
superior
replicative
ability
32°C
and
30°C,
whereas
most
other
Omicron
sub-variant
isolates
limited
growth.
Deep
sequencing
analysis
demonstrated
that
frequencies
viruses
possessing
NSP6-S163P
NSP13-P238S
substitutions
increased
to
more
than
97%
during
propagation
did
not
reach
55%
37°C.
Reverse
genetics
revealed
these
contributed
virus
growth
vitro
low
temperatures
by
improving
genome
replication.
Mutant
both
slightly
higher
titers
hamsters
compared
parental
virus;
however,
transmissibility
between
was
similar
for
mutant
viruses.
Taken
together,
our
findings
indicate
contribute
hamsters.
IMPORTANCE
Severe
efficiently
However,
airway
30°C–32°C.
Therefore,
could
influence
we
assessed
sub-variants
found
ability.
By
deep
reverse
genetics,
amino
acid
changes
NSP6
NSP13
low-temperature
growth;
improved
RNA
polymerase
activity
enhanced
Although
alone
drastically
transmissibility,
combination
with
substitutions,
they
humans.
Furthermore,
since
enhance
cultured
cells,
be
used
improve
production
inactivated
or
live
attenuated
vaccine
virus.
Language: Английский
The NSP6-L260F substitution in SARS-CoV-2 BQ.1.1 and XBB.1.16 lineages compensates for the reduced viral polymerase activity caused by mutations in NSP13 and NSP14
Journal of Virology,
Journal Year:
2025,
Volume and Issue:
unknown
Published: May 13, 2025
ABSTRACT
Severe
acute
respiratory
syndrome
coronavirus
2
(SARS-CoV-2)
Omicron
variants
emerged
at
the
end
of
2021,
and
their
subvariants
are
still
circulating
worldwide.
While
changes
in
S
protein
these
have
been
extensively
studied,
roles
amino
acid
substitutions
non-structural
proteins
not
fully
revealed.
In
this
study,
we
found
that
SARS-CoV-2
bearing
NSP6-L260F
substitution
repeatedly
when
generated
several
by
reverse
genetics
or
passaged
isolated
from
clinical
samples
it
was
selected
under
cell
culture
conditions.
Although
has
detected
BQ.1.1
XBB.1.16
circulated
nature,
its
effect
on
viral
properties
is
unclear.
Here,
with
without
promotes
virus
replication
vitro
vivo
increasing
polymerase
activity
enhancing
pathogenicity
hamsters.
We
also
identified
disadvantageous
substitutions,
NSP13-M233I
NSP14-D222Y,
reduced
replication,
respectively.
These
adverse
effects
were
compensated
for
NSP6-L260F.
Our
findings
suggest
importance
reveal
part
evolutionary
process
variants.
IMPORTANCE
severe
continue
to
change
through
acquisition
various
explored.
enhances
important
pathogenicity.
addition,
lineage
NSP14-D222Y
reduce
activity,
substitution.
results
provide
insight
into
SARS-CoV-2.
Language: Английский
Immunogenicity and safety of a live-attenuated SARS-CoV-2 vaccine candidate based on multiple attenuation mechanisms
Mie Suzuki-Okutani,
No information about this author
Shinya Okamura,
No information about this author
Tang Gis
No information about this author
et al.
eLife,
Journal Year:
2024,
Volume and Issue:
13
Published: April 26, 2024
mRNA
vaccines
against
SARS-CoV-2
were
rapidly
developed
and
effective
during
the
pandemic.
However,
some
limitations
remain
to
be
resolved,
such
as
short-lived
induced
immune
response
certain
adverse
effects.
Therefore,
there
is
an
urgent
need
develop
new
that
address
these
issues.
While
live-attenuated
are
a
highly
modality,
they
pose
risk
of
effects,
including
virulence
reversion.
In
current
study,
we
constructed
vaccine
candidate,
BK2102,
combining
naturally
occurring
virulence-attenuating
mutations
in
NSP14
,
NSP1
spike,
ORF7-8
coding
regions.
Intranasal
inoculation
with
BK2102
humoral
cellular
responses
Syrian
hamsters
without
apparent
tissue
damage
lungs,
leading
protection
D614G
Omicron
BA.5
strains.
The
neutralizing
antibodies
by
persisted
for
up
364
days,
which
indicated
confer
long-term
infection.
Furthermore,
confirmed
safety
using
transgenic
(Tg)
mice
expressing
human
ACE2
(hACE2)
susceptible
SARS-CoV-2.
did
not
kill
Tg
mice,
even
when
virus
was
administered
at
dose
10
6
plaque-forming
units
(PFUs),
while
2
PFU
strain
or
attenuated
lacking
furin
cleavage
site
spike
sufficient
mice.
These
results
suggest
promising
live-vaccine
candidate
confers
significant
virulence.
Language: Английский
Immunogenicity and safety of a live-attenuated SARS-CoV-2 vaccine candidate based on multiple attenuation mechanisms
Mie Suzuki-Okutani,
No information about this author
Shinya Okamura,
No information about this author
Tanggis
No information about this author
et al.
bioRxiv (Cold Spring Harbor Laboratory),
Journal Year:
2024,
Volume and Issue:
unknown
Published: March 4, 2024
Abstract
mRNA
vaccines
against
SARS-CoV-2
were
rapidly
developed
and
effective
during
the
pandemic.
However,
some
limitations
remain
to
be
resolved,
such
as
short-lived
induced
immune
response
certain
adverse
effects.
Therefore,
there
is
an
urgent
need
develop
new
that
address
these
issues.
While
live-attenuated
are
a
highly
modality,
they
pose
risk
of
effects,
including
virulence
reversion.
In
current
study,
we
constructed
vaccine
candidate,
BK2102,
combining
naturally
occurring
virulence-attenuating
mutations
in
NSP14
,
NSP1
spike
ORF7-8
coding
regions.
Intranasal
inoculation
with
BK2102
humoral
cellular
responses
Syrian
hamsters
without
apparent
tissue
damage
lungs,
leading
protection
D614G
Omicron
BA.5
strains.
The
neutralizing
antibodies
by
persisted
for
up
364
days,
which
indicated
confer
long-term
infection.
Furthermore,
confirmed
safety
using
transgenic
(Tg)
mice
expressing
human
ACE2
(hACE2),
susceptible
SARS-CoV-2.
did
not
kill
Tg
mice,
even
when
virus
was
administered
at
dose
10
6
plaque-forming
units
(PFU),
while
2
PFU
strain
or
attenuated
lacking
furin
cleavage
site
(FCS)
sufficient
mice.
These
results
suggest
promising
live-vaccine
candidate
confers
significant
virulence.
Language: Английский
Amino acid T25 in the substrate-binding domain of SARS-CoV-2 nsp5 is involved in viral replication in the mouse lung
Yoshiro Sugiura,
No information about this author
Kenta Shimizu,
No information about this author
Tatsuki Takahashi
No information about this author
et al.
PLoS ONE,
Journal Year:
2024,
Volume and Issue:
19(12), P. e0312800 - e0312800
Published: Dec. 6, 2024
Severe
acute
respiratory
syndrome
coronavirus
2
(SARS-CoV-2)
non-structural
protein
5
(nsp5)
is
a
cysteine
protease
involved
in
viral
replication
and
suppression
of
the
host
immune
system.
The
substrate-binding
domain
nsp5
important
for
its
activity.
However,
relationship
between
activity
remains
unclear.
We
confirmed
importance
amino
acid
T25
using
split
luciferase
assay.
By
generating
recombinant
viruses
bacterial
artificial
chromosomes,
we
found
that
proliferation
with
T25I
mutation
was
cell-dependent
culture.
Furthermore,
mice
infected
mutant
virus
mouse
acclimation
backbone
showed
weight
loss
increased
lung
load,
similar
to
wild-type
(WT)
group,
up
3
days
after
infection.
day
4,
load
significantly
reduced
T25I-infected
group
compared
WT-infected
group.
This
suggests
pathogenesis
SARS-CoV-2.
Language: Английский