Nature Medicine,
Journal Year:
2023,
Volume and Issue:
29(10), P. 2547 - 2558
Published: Sept. 11, 2023
Abstract
Inducing
antiretroviral
therapy
(ART)-free
virological
control
is
a
critical
step
toward
human
immunodeficiency
virus
type
1
(HIV-1)
cure.
In
this
phase
2a,
placebo-controlled,
double-blinded
trial,
43
people
(85%
males)
with
HIV-1
on
ART
were
randomized
to
(1)
placebo/placebo,
(2)
lefitolimod
(TLR9
agonist)/placebo,
(3)
placebo/broadly
neutralizing
anti-HIV-1
antibodies
(bNAbs)
or
(4)
lefitolimod/bNAb.
interruption
(ATI)
started
at
week
3.
Lefitolimod
was
administered
once
weekly
for
the
first
8
weeks,
and
bNAbs
twice,
d
before
3
weeks
after
ATI.
The
primary
endpoint
time
loss
of
virologic
median
delay
in
compared
placebo/placebo
group
0.5
(
P
=
0.49),
12.5
0.003)
9.5
0.004)
lefitolimod/placebo,
placebo/bNAb
lefitolimod/bNAb
groups,
respectively.
Among
secondary
endpoints,
viral
doubling
slower
bNAb
groups
non-bNAb
interventions
overall
safe.
We
observed
no
added
benefit
lefitolimod.
Despite
subtherapeutic
plasma
levels,
36%
(4/11)
0%
(0/10)
maintained
25-week
Although
immunotherapy
did
not
lead
ART-free
control,
may
be
important
components
future
curative
strategies.
ClinicalTrials.gov
identifier:
NCT03837756
.
Frontiers in Immunology,
Journal Year:
2019,
Volume and Issue:
10
Published: June 7, 2019
Antibodies
and
Fc-fusion
antibody-like
proteins
have
become
successful
biologics
developed
for
cancer
treatment,
passive
immunity
against
infection,
addiction,
autoimmune
diseases.
In
general
these
biopharmaceuticals
can
be
used
blocking
protein:protein
interactions,
crosslinking
host
receptors
to
induce
signaling,
recruiting
effector
cells
targets,
fixing
complement.
With
the
vast
capability
of
antibodies
affect
infectious
genetic
diseases
much
effort
has
been
placed
on
improving
tailoring
specific
functions.
While
antibody:antigen
engagement
is
critical
an
efficacious
antibody
biologic,
equally
as
important
are
hinge
constant
domains
heavy
chain.
It
that
engage
or
complement
protein
mediate
a
myriad
functions
regulate
circulation.
Molecular
structural
studies
provided
insight
into
how
from
across
different
species,
isotypes,
subclasses,
alleles
recognized
by
cell
C1q.
The
molecular
details
interactions
led
manipulation
sequences
glycosylation
enhance
reduce
circulating
half-life.
This
review
will
describe
concepts
being
applied
optimize
crystallizable
fragment
antibodies,
it
detail
tuned
up
down
biological
function
confers
desired
disease
outcome.
Nature Reviews Drug Discovery,
Journal Year:
2022,
Volume and Issue:
21(9), P. 676 - 696
Published: June 20, 2022
Monoclonal
antibodies
(mAbs)
are
appealing
as
potential
therapeutics
and
prophylactics
for
viral
infections
owing
to
characteristics
such
their
high
specificity
ability
enhance
immune
responses.
Furthermore,
antibody
engineering
can
be
used
strengthen
effector
function
prolong
mAb
half-life,
advances
in
structural
biology
have
enabled
the
selection
optimization
of
potent
neutralizing
mAbs
through
identification
vulnerable
regions
proteins,
which
also
relevant
vaccine
design.
The
COVID-19
pandemic
has
stimulated
extensive
efforts
develop
against
severe
acute
respiratory
syndrome
coronavirus
2
(SARS-CoV-2),
with
several
now
having
received
authorization
emergency
use,
providing
not
just
an
important
component
strategies
combat
but
a
boost
harness
therapeutic
preventive
settings
other
infectious
diseases.
Here,
we
describe
discovery
that
led
development
use
caused
by
viruses
including
SARS-CoV-2,
syncytial
virus
(RSV),
Ebola
(EBOV),
human
cytomegalovirus
(HCMV)
influenza.
We
discuss
rationale
moving
from
empirical
structure-guided
development,
based
on
identifying
optimal
candidate
antigens
within
them
targeted
result
strong
protective
response.
