The
severe
acute
respiratory
coronavirus-2
(SARS-CoV-2)
is
the
cause
of
global
outbreak
COVID-19.
Evidence
suggests
that
virus
evolving
to
allow
efficient
spread
through
human
population,
including
vaccinated
individuals.
Here,
we
report
a
study
viral
variants
from
surveillance
Delaware
Valley,
city
Philadelphia,
and
infecting
subjects.
We
sequenced
analyzed
complete
genomes
2621
samples
March
2020
September
2021
compared
them
genome
sequences
159
vaccine
breakthroughs.
In
early
spring
2020,
all
detected
were
B.1
closely
related
lineages.
A
mixture
lineages
followed,
notably
B.1.243
followed
by
B.1.1.7
(alpha),
with
other
present
at
lower
levels.
Later
isolations
dominated
B.1.617.2
(delta)
delta
lineages;
was
exclusive
variant
last
time
sampled.
To
investigate
whether
any
appeared
preferentially
in
breakthroughs,
devised
model
based
on
Bayesian
autoregressive
moving
average
logistic
multinomial
regression
rigorous
comparison.
This
revealed
showed
3-fold
enrichment
breakthrough
cases
(odds
ratio
3;
95%
credible
interval
0.89-11).
Viral
point
substitutions
could
also
be
associated
N501Y
substitution
found
alpha,
beta
gamma
2.04;
of1.25-3.18).
thus
overviews
evolution
breakthroughs
Valley
introduces
statistical
approach
interrogating
against
changing
background.
Nature Medicine,
Journal Year:
2022,
Volume and Issue:
28(7), P. 1501 - 1508
Published: June 20, 2022
Abstract
In
some
immunocompromised
patients
with
chronic
severe
acute
respiratory
syndrome
coronavirus
2
(SARS-CoV-2)
infection,
considerable
adaptive
evolution
occurs.
Some
substitutions
found
in
infections
are
lineage-defining
mutations
variants
of
concern
(VOCs),
which
has
led
to
the
hypothesis
that
VOCs
emerged
from
infections.
this
study,
we
searched
for
drivers
VOC-like
emergence
by
consolidating
sequencing
results
a
set
27
Most
reflected
VOC
mutations;
however,
subset
associated
successful
global
transmission
was
absent
We
further
tested
ability
associate
antibody
evasion
patient-specific
and
virus-specific
features
viral
rebound
is
strongly
correlated
evasion.
evidence
dynamic
polymorphic
populations
most
patients,
suggesting
compromised
immune
system
selects
particular
niches
patient’s
body.
suggest
tradeoff
exists
between
transmissibility
extensive
monitoring
necessary
understanding
emergence.
Science Immunology,
Journal Year:
2022,
Volume and Issue:
7(78)
Published: Nov. 10, 2022
Numerous
safe
and
effective
coronavirus
disease
2019
vaccines
have
been
developed
worldwide
that
use
various
delivery
technologies
engineering
strategies.
We
show
here
containing
prefusion-stabilizing
S
mutations
elicit
antibody
responses
in
humans
with
enhanced
recognition
of
the
PLoS Pathogens,
Journal Year:
2022,
Volume and Issue:
18(2), P. e1010248 - e1010248
Published: Feb. 8, 2022
Many
SARS-CoV-2
variants
have
mutations
at
key
sites
targeted
by
antibodies.
However,
it
is
unknown
if
antibodies
elicited
infection
with
these
target
the
same
or
different
regions
of
viral
spike
as
earlier
isolates.
Here
we
compare
specificities
polyclonal
produced
humans
infected
early
2020
isolates
versus
B.1.351
variant
concern
(also
known
Beta
20H/501Y.V2),
which
contains
in
multiple
epitopes.
The
serum
neutralizing
activity
both
viruses
and
heavily
focused
on
receptor-binding
domain
(RBD).
within
RBD,
B.1.351-elicited
are
more
"class
3"
epitope
spanning
443
to
452,
neutralization
notably
less
affected
residue
484.
Our
results
show
that
can
elicit
immunodominance
hierarchies.
Virus Evolution,
Journal Year:
2022,
Volume and Issue:
8(2)
Published: July 1, 2022
Abstract
Continued
evolution
and
adaptation
of
SARS-CoV-2
has
led
to
more
transmissible
immune-evasive
variants
with
profound
impacts
on
the
course
pandemic.
Here
I
analyze
virus
over
2.5
years
since
its
emergence
estimate
rates
for
synonymous
non-synonymous
changes
separately
within
clades—well-defined
monophyletic
groups
gradual
evolution—and
pandemic
overall.
The
rate
mutation
is
found
be
around
6
per
year.
Synonymous
vary
little
from
variant
are
compatible
overall
7
year
(or
$7.5
\times
10^{-4}$
codon).
In
contrast,
at
which
accumulate
amino
acid
(non-synonymous
mutations)
was
initially
12-16
year,
but
in
2021
2022
it
dropped
6-9
evolution,
that
across
variants,
estimated
about
26
$2.7
10^{-3}$
This
strong
acceleration
compared
clade
indicates
evolutionary
process
gave
rise
different
qualitatively
typical
transmission
chains
likely
dominated
by
adaptive
evolution.
further
quantify
spectrum
mutations
purifying
selection
proteins
show
massive
global
sampling
sufficient
site-specific
fitness
costs
entire
genome.
Many
accessory
evolve
under
limited
constraints
short-term
selection.
About
half
other
strongly
deleterious.
Genes,
Journal Year:
2023,
Volume and Issue:
14(2), P. 407 - 407
Published: Feb. 4, 2023
The
severe
acute
respiratory
syndrome
coronavirus
2
(SARS-CoV-2)
produced
diverse
molecular
variants
during
its
recent
expansion
in
humans
that
caused
different
transmissibility
and
severity
of
the
associated
disease
as
well
resistance
to
monoclonal
antibodies
polyclonal
sera,
among
other
treatments.
In
order
understand
causes
consequences
observed
SARS-CoV-2
diversity,
a
variety
studies
investigated
evolution
this
virus
humans.
general,
evolves
with
moderate
rate
evolution,
10
Cell Host & Microbe,
Journal Year:
2023,
Volume and Issue:
31(11), P. 1898 - 1909.e3
Published: Oct. 25, 2023
Through
antigenic
evolution,
viruses
such
as
seasonal
influenza
evade
recognition
by
neutralizing
antibodies.
This
means
that
a
person
with
antibodies
well
tuned
to
an
initial
infection
will
not
be
protected
against
the
same
virus
years
later
and
vaccine-mediated
protection
decay.
To
expand
our
understanding
of
which
endemic
human
evolve
in
this
fashion,
we
assess
adaptive
evolution
across
genome
28
spanning
wide
range
viral
families
transmission
modes.
Surface
proteins
consistently
show
highest
rates
adaptation,
ten
panel
are
estimated
undergo
selectively
fix
mutations
enable
escape
prior
immunity.
Thus,
antibody
evasion
is
uncommon
evolutionary
strategy
among
viruses,
monitoring
inform
future
vaccine
efforts.
Additionally,
comparing
overall
amino
acid
substitution
rates,
SARS-CoV-2
accumulating
protein-coding
changes
at
substantially
faster
than
viruses.
Nature Communications,
Journal Year:
2024,
Volume and Issue:
15(1)
Published: Feb. 20, 2024
Abstract
Ever-evolving
SARS-CoV-2
variants
of
concern
(VOCs)
have
diminished
the
effectiveness
therapeutic
antibodies
and
vaccines.
Developing
a
coronavirus
vaccine
that
offers
greater
breadth
protection
against
current
future
VOCs
would
eliminate
need
to
reformulate
COVID-19
Here,
we
rationally
engineer
sequence-conserved
S2
subunit
spike
protein
characterize
resulting
S2-only
antigens.
Structural
studies
demonstrate
introduction
interprotomer
disulfide
bonds
can
lock
in
prefusion
trimers,
although
apex
samples
continuum
conformations
between
open
closed
states.
Immunization
with
prefusion-stabilized
constructs
elicits
broadly
neutralizing
responses
several
sarbecoviruses
protects
female
BALB/c
mice
from
mouse-adapted
lethal
challenge
partially
SARS-CoV
challenge.
These
engineering
immunogenicity
results
should
inform
development
next-generation
pan-coronavirus
therapeutics
Nature Communications,
Journal Year:
2024,
Volume and Issue:
15(1)
Published: March 15, 2024
Abstract
SARS-CoV-2
clearance
requires
adaptive
immunity
but
the
contribution
of
neutralizing
antibodies
and
T
cells
in
different
immune
states
is
unclear.
Here
we
ask
which
responses
associate
with
long-term
infection
HIV-mediated
immunosuppression
after
suppressive
antiretroviral
therapy
(ART)
initiation.
We
assembled
a
cohort
infected
people
South
Africa
(
n
=
994)
including
participants
advanced
HIV
disease
characterized
by
due
to
cell
depletion.
Fifty-four
percent
had
prolonged
(>1
month).
In
five
vaccinated
tested,
associates
emergence
not
specific
CD8
cells,
while
CD4
were
determined
low
numbers.
Further,
complete
suppression
required
for
clearance,
although
it
necessary
an
effective
vaccine
response.
Persistent
led
evolution,
virus
extensive
neutralization
escape
Delta
variant
participant.
The
results
provide
evidence
that
are
recovery,
ART
curtail
evolution
co-infecting
pathogens
reduce
individual
health
consequences
as
well
public
risk
linked
generation
mutants.