bioRxiv (Cold Spring Harbor Laboratory),
Год журнала:
2023,
Номер
unknown
Опубликована: Сен. 13, 2023
Although
Rhinolophus
bats
harbor
diverse
clade
3
sarbecoviruses,
the
structural
determinants
of
receptor
tropism
along
with
antigenicity
their
spike
(S)
glycoproteins
remain
uncharacterized.
Here,
we
show
that
African
Rinolophus
bat
sarbecovirus
PRD-0038
S
has
a
broad
ACE2
usage
and
RBD
mutations
further
expand
promiscuity
enable
human
utilization.
We
determined
cryoEM
structure
bound
to
R.
alcyone
ACE2,
explaining
highlighting
differences
SARS-CoV-1
SARS-CoV-2.
Characterization
using
monoclonal
antibody
reactivity
revealed
its
distinct
relative
SARS-CoV-2
identified
cross-neutralizing
antibodies
for
pandemic
preparedness.
vaccination
elicited
greater
titers
cross-reacting
vaccine-mismatched
2
1a
sarbecoviruses
compared
due
broader
antigenic
targeting,
motivating
inclusion
antigens
in
next-generation
vaccines
enhanced
resilience
viral
evolution.
Frontiers in Immunology,
Год журнала:
2023,
Номер
14
Опубликована: Май 12, 2023
Introduction
Chikungunya
virus
(CHIKV)
is
a
re-emerging
mosquito
transmitted
alphavirus
of
global
concern.
Neutralizing
antibodies
and
antibody
Fc-effector
functions
have
been
shown
to
reduce
CHIKV
disease
infection
in
animals.
However,
the
ability
improve
therapeutic
activity
CHIKV-specific
polyclonal
IgG
by
enhancing
through
modulation
subclass
glycoforms
remains
unknown.
Here,
we
evaluated
protective
efficacy
CHIKV-immune
enriched
for
binding
Fc-gamma
receptor
IIIa
(FcγRIIIa)
select
with
enhanced
Fc
effector
functions.
Methods
Total
was
isolated
from
convalescent
donors
without
additional
purification
FcγRIIIa
affinity
chromatography.
The
characterized
biophysical
biological
assays
assessed
during
mice.
Results
FcγRIIIa-column
afucosylated
glycoforms.
In
vitro
characterization
showed
had
human
mouse
FcγRIV
FcγR-mediated
function
reducing
neutralization
cellular
assays.
When
administered
as
post-exposure
therapy
mice,
promoted
reduction
viral
load.
Discussion
Our
study
provides
evidence
that,
increasing
engagement
FcγRs
on
cells,
leveraging
FcγRIIIa-affinity
chromatography,
antiviral
reveals
path
produce
more
effective
therapeutics
against
these
potentially
other
emerging
viruses.
iScience,
Год журнала:
2024,
Номер
27(9), С. 110174 - 110174
Опубликована: Июнь 5, 2024
Antibodies
represent
a
primary
mediator
of
protection
against
respiratory
viruses.
Serum
neutralizing
antibodies
(NAbs)
are
often
considered
correlate
protection.
However,
detailed
antibody
profiles
including
characterization
functions
in
different
anatomic
compartments
poorly
understood.
Here
we
show
that
correlates
severe
acute
syndrome
coronavirus
2
(SARS-CoV-2)
challenge
systemic
versus
mucosal
rhesus
macaques.
In
serum,
NAbs
were
the
strongest
and
linked
to
spike-specific
binding
other
extra-NAb
create
larger
protective
network.
bronchiolar
lavage
(BAL),
antibody-dependent
cellular
phagocytosis
(ADCP)
proved
rather
than
NAbs.
Within
BAL,
ADCP
was
immunoglobulin
(Ig)G,
IgA/secretory
IgA,
Fcγ-receptor
antibodies.
Our
results
support
model
which
with
mediate
at
sites.
bioRxiv (Cold Spring Harbor Laboratory),
Год журнала:
2023,
Номер
unknown
Опубликована: Сен. 13, 2023
Although
Rhinolophus
bats
harbor
diverse
clade
3
sarbecoviruses,
the
structural
determinants
of
receptor
tropism
along
with
antigenicity
their
spike
(S)
glycoproteins
remain
uncharacterized.
Here,
we
show
that
African
Rinolophus
bat
sarbecovirus
PRD-0038
S
has
a
broad
ACE2
usage
and
RBD
mutations
further
expand
promiscuity
enable
human
utilization.
We
determined
cryoEM
structure
bound
to
R.
alcyone
ACE2,
explaining
highlighting
differences
SARS-CoV-1
SARS-CoV-2.
Characterization
using
monoclonal
antibody
reactivity
revealed
its
distinct
relative
SARS-CoV-2
identified
cross-neutralizing
antibodies
for
pandemic
preparedness.
vaccination
elicited
greater
titers
cross-reacting
vaccine-mismatched
2
1a
sarbecoviruses
compared
due
broader
antigenic
targeting,
motivating
inclusion
antigens
in
next-generation
vaccines
enhanced
resilience
viral
evolution.
