Clonal Interference and Changing Selective Pressures Shape the Escape of Sars-Cov-2 from Hundreds of Antibodies
Опубликована: Янв. 1, 2025
Язык: Английский
Deep mutational scanning and CRISPR-engineered viruses: tools for evolutionary and functional genomics studies
mSphere,
Год журнала:
2025,
Номер
unknown
Опубликована: Апрель 24, 2025
ABSTRACT
Recent
advancements
in
synthetic
biology
and
sequencing
technologies
have
revolutionized
the
ability
to
manipulate
viral
genomes
with
unparalleled
precision.
This
review
focuses
on
two
powerful
methodologies:
deep
mutational
scanning
CRISPR-based
genome
editing,
that
enable
comprehensive
mutagenesis
detailed
functional
characterization
of
proteins.
These
approaches
significantly
deepened
our
understanding
molecular
determinants
driving
evolution
adaptation.
Furthermore,
we
discuss
how
these
advances
provide
transformative
insights
for
future
vaccine
development
therapeutic
strategies.
Язык: Английский
Structure-guided design of a prefusion GPC trimer induces neutralizing responses against LASV
npj Vaccines,
Год журнала:
2025,
Номер
10(1)
Опубликована: Фев. 22, 2025
Lassa
virus
(LASV)
belongs
to
the
Arenaviridae
family
and
causes
severe
hemorrhagic
fever
in
humans.
Although
many
vaccine
candidates
for
exist,
no
vaccines
have
been
approved
clinical
use
currently.
The
precursor
glycoprotein
complex
(GPC),
which
is
expressed
as
a
trimer
on
viral
surface,
main
target
development.
However,
it
has
significant
challenge
elicit
effective
neutralizing
antibodies
against
LASV.
In
this
study,
we
designed
produced
prefusion
GPC
antigen
of
LASV,
named
GPCv2.
Based
structural
information
GPC,
made
modifications
by
replacing
amino
acid
at
position
328
with
proline
appending
trimerization
domain.
This
resulted
highly
trimeric
form
GPCv2
that
retained
important
conformational
epitopes
stimulated
higher
levels
antibodies.
Moreover,
vaccination
protected
mice
from
LASV
pseudovirus
challenge.
Additionally,
immune
repertoire
sequencing
showed
induced
clones
group
were
more
convergent
its
own
unique
V-J
pairing
bias
compared
monomeric
group.
These
findings
demonstrate
potential
promising
candidate
an
Язык: Английский
Deep mutational scanning of rabies glycoprotein defines mutational constraint and antibody-escape mutations
bioRxiv (Cold Spring Harbor Laboratory),
Год журнала:
2024,
Номер
unknown
Опубликована: Дек. 17, 2024
Abstract
Rabies
virus
causes
nearly
60,000
human
deaths
annually.
Antibodies
that
target
the
rabies
glycoprotein
(G)
are
being
developed
as
post-exposure
prophylactics,
but
mutations
in
G
can
render
such
antibodies
ineffective.
Here,
we
use
pseudovirus
deep
mutational
scanning
to
measure
how
all
single
amino-acid
affect
cell
entry
and
neutralization
by
a
panel
of
antibodies.
These
measurements
identify
sites
critical
for
G’s
function,
define
constrained
regions
attractive
epitopes
clinical
antibodies,
including
at
apex
base
protein.
We
provide
complete
maps
escape
eight
monoclonal
some
or
development.
Escape
most
present
natural
strains.
Overall,
this
work
provides
comprehensive
information
on
functional
antigenic
effects
help
inform
development
stabilized
vaccine
antigens
resilient
genetic
variation.
Язык: Английский
Machine Learning Reveals Key Glycoprotein Mutations and Rapidly Assigns Lassa Virus Lineages
bioRxiv (Cold Spring Harbor Laboratory),
Год журнала:
2024,
Номер
unknown
Опубликована: Июль 31, 2024
Abstract
Lassa
fever,
caused
by
the
virus
(LASV),
remains
a
major
public
health
concern
in
West
Africa,
causing
numerous
fatalities
annually
and
several
intercontinental
cases
since
its
discovery
1969.
Despite
ongoing
research,
no
approved
vaccines
are
available,
with
current
efforts
focusing
on
immunotherapy.
LASV
is
divided
into
distinct
lineages
that
circulate
specific
geographic
regions,
elicit
varying
immune
responses,
exhibit
different
pathophysiological
effects.
Understanding
genetic
differences
between
these
crucial
for
developing,
improving,
distributing
diagnostics,
treatments,
vaccines.
In
this
study,
we
analyzed
glycoprotein
complex
(GPC),
only
surface
protein,
using
statistics,
machine
learning,
phylogenetics.
At
population
scale,
identified
key
amino
acid
Nigerian
those
other
African
particularly
near
stable
signal
peptide
cleavage
site
immune-related
regions
(e.g.,
AA
positions
59–76).
Additionally,
found
GPC
sequences
from
Lineages
II
III
shorter
than
Lineage
IV,
due
to
high
prevalence
of
codon
insertion
at
178–180
(amino
position
60).
This
may
contribute
inaccuracies
observed
molecular
diagnostics
also
play
role
increased
fatality
associated
IV.
The
has
reemerged
persisted
which
indicate
fitness
advantage.
Furthermore,
developed
fast
highly
accurate
lineage
classification
tool
called
CLASV
allows
rapid
identification
lineages,
improving
ability
monitor
emerging
outbreaks
exported
cases.
Язык: Английский
A validated and standardized pseudotyped microneutralization assay as a safe and powerful tool to measure LASSA virus neutralising antibodies for vaccine development and comparison
F1000Research,
Год журнала:
2024,
Номер
13, С. 534 - 534
Опубликована: Окт. 14, 2024
Over
the
past
few
decades,
World
Health
Organization
(WHO)
has
made
massive
efforts
to
promote
development
of
a
vaccine
against
Lassa
virus
(LASV),
one
top
ten
priority
pathogens
for
research
and
under
WHO
R&D
Blueprint
Emerging
Infections.
To
date,
several
vaccines
are
at
different
stages
development.
In
this
scenario,
validated
standardised
assay
measure
LASV
neutralising
antibodies
is
urgently
needed
comparison.
Язык: Английский