Progress and Challenges in HIV-1 Vaccine Research: A Comprehensive Overview
Vaccines,
Год журнала:
2025,
Номер
13(2), С. 148 - 148
Опубликована: Янв. 31, 2025
The
development
of
an
effective
HIV-1
vaccine
remains
a
formidable
challenge
in
biomedical
research.
Despite
significant
advancements
our
understanding
HIV
biology
and
pathogenesis,
progress
has
been
impeded
by
factors
such
as
the
virus's
genetic
diversity,
high
mutation
rates,
its
ability
to
establish
latent
reservoirs.
Recent
innovative
approaches,
including
mosaic
vaccines
mRNA
technology
induce
broadly
neutralizing
antibodies,
have
shown
promise.
However,
efficacy
these
modest,
with
best
results
achieving
approximately
30%
effectiveness.
Ongoing
research
emphasizes
necessity
multifaceted
strategy
overcome
obstacles
achieve
breakthrough
development.
This
review
summarizes
current
approaches
utilized
further
understand
create
global
vaccine.
We
discuss
impact
on
for
other
diseases,
COVID-19,
influenza,
Zika
virus.
Additionally,
we
highlight
specific
limitations
faced
each
approach
present
methods
researchers
employ
challenges.
These
techniques,
which
demonstrated
preclinical
clinical
success,
advanced
field
closer
ultimate
goal
developing
Leveraging
will
enable
strides
combating
infectious
ultimately
improving
health
outcomes.
Язык: Английский
mRNA-LNP prime boost evolves precursors toward VRC01-like broadly neutralizing antibodies in preclinical humanized mouse models
Science Immunology,
Год журнала:
2024,
Номер
9(95)
Опубликована: Май 10, 2024
Germline-targeting
(GT)
protein
immunogens
to
induce
VRC01-class
broadly
neutralizing
antibodies
(bnAbs)
the
CD4-binding
site
of
HIV
envelope
(Env)
have
shown
promise
in
clinical
trials.
Here,
we
preclinically
validated
a
lipid
nanoparticle-encapsulated
nucleoside
mRNA
(mRNA-LNP)
encoding
eOD-GT8
60mer
as
soluble
self-assembling
nanoparticle
mouse
models.
In
model
with
three
humanized
B
cell
lineages
bearing
distinct
VRC01-precursor
receptors
(BCRs)
similar
affinities
for
eOD-GT8,
all
could
be
simultaneously
primed
and
undergo
diversification
affinity
maturation
without
exclusionary
competition.
Boosts
drove
precursor
participation
germinal
centers;
accumulation
somatic
hypermutations,
including
key
positions;
boost
native-like
antigens
two
lineages.
We
prime-boost
regimen
nanoparticles
encoded
by
mRNA-LNP,
demonstrating
that
multiple
can
primed,
boosted,
diversified
along
bnAb
pathway.
Язык: Английский
Interventions during Early Infection: Opening a Window for an HIV Cure?
Viruses,
Год журнала:
2024,
Номер
16(10), С. 1588 - 1588
Опубликована: Окт. 9, 2024
Although
combination
antiretroviral
therapy
(ART)
has
been
a
landmark
achievement
for
the
treatment
of
human
immunodeficiency
virus
(HIV),
an
HIV
cure
remained
elusive.
Elimination
latent
reservoirs
that
persist
throughout
infection
is
most
challenging
barrier
to
cure.
The
progressive
marked
by
increasing
size
and
diversity
until
effective
immune
response
mobilized,
which
can
control
but
not
eliminate
infection.
stalemate
between
replication
manifested
establishment
viral
set
point.
ART
initiation
during
early
stage
limits
reservoir
development,
preserves
function,
improves
quality
life,
may
lead
ART-free
remission
in
few
people
living
with
(PLWH).
However,
overwhelming
majority
PLWH,
alone
does
HIV,
lifelong
needed
sustain
suppression.
A
critical
area
research
focused
on
determining
whether
could
be
functionally
cured
if
additional
treatments
are
provided
alongside
ART.
Several
interventions
including
Block
Lock,
Shock
Kill,
broadly
neutralizing
antibody
(bNAb)
therapy,
adoptive
CD8+
T
cell
gene
have
demonstrated
delayed
rebound
and/or
animal
models
some
PLWH.
Whether
or
their
application
improve
success
less
studied.
Herein,
we
review
current
state
clinical
investigative
discuss
potential
likelihood
post-treatment
initiated
Язык: Английский
The Fight Continues: Virus Without Vaccines
Опубликована: Янв. 1, 2025
Язык: Английский
Vaccination with mRNA-encoded nanoparticles drives early maturation of HIV bnAb precursors in humans
Science,
Год журнала:
2025,
Номер
unknown
Опубликована: Май 15, 2025
A
leading
HIV
vaccine
strategy
requires
a
priming
immunogen
to
induce
broadly
neutralizing
antibody
(bnAb)
precursors,
followed
by
series
of
heterologous
boosters
elicit
somatic
hypermutation
(SHM)
and
produce
bnAbs.
In
two
randomized,
open-label
phase
1
human
clinical
trials,
IAVI-G002
in
the
United
States
IAVI-G003
Rwanda
South
Africa,
we
evaluated
safety
immunogenicity
mRNA-encoded
nanoparticles
as
immunogens
(both
trials)
first-boosting
(IAVI-G002).
The
vaccines
were
generally
safe
well
tolerated,
except
18%
participants
experienced
skin
reactions.
Priming
induced
bnAb
precursors
with
substantial
frequencies
SHM,
boosting
elicited
increased
affinity,
neutralization
activity
toward
development.
results
establish
proof
concept
that
can
advance
bnAb-precursor
maturation
demonstrate
Africa
where
burden
is
highest.
Язык: Английский
Advancing Human Vaccine Development Using Humanized Mouse Models
Vaccines,
Год журнала:
2024,
Номер
12(9), С. 1012 - 1012
Опубликована: Сен. 4, 2024
The
development
of
effective
vaccines
against
infectious
diseases
remains
a
critical
challenge
in
global
health.
Animal
models
play
crucial
role
vaccine
by
providing
valuable
insights
into
the
efficacy,
safety,
and
mechanisms
immune
response
induction,
which
guide
design
formulation
vaccines.
However,
traditional
animal
often
inadequately
recapitulate
human
responses.
Humanized
mice
(hu-mice)
with
functional
system
have
emerged
as
invaluable
tools
bridging
translational
gap
between
preclinical
research
clinical
trials
for
development.
This
review
summarizes
commonly
used
hu-mice
advances
optimizing
them
to
improve
We
application
humanized
focus
on
HIV-1
also
discuss
remaining
challenges
improvements
needed
currently
available
better
facilitate
testing
diseases.
Язык: Английский
mRNA Vaccines for HIV‐1
Опубликована: Дек. 6, 2024
The
development
of
a
protective
vaccine
for
HIV-1
represents
one
the
most
formidable
challenges
modern
science.
Despite
long
series
failures
over
past
40
years,
accruing
evidence
indicates
that
an
is
feasible.
recent
encounter
between
field
and
messenger
RNA
(mRNA)
technology
has
opened
new
perspectives
to
accelerate
discovery.
extraordinary
efficiency
versatility
mRNA,
coupled
with
its
ability
induce
endogenous
expression
bona
fide
native
envelope
trimers,
offer
specific
benefits
vaccine,
as
confirmed
by
results
preclinical
studies.
Язык: Английский
Beyond glycan barriers: non-cognate ligands and protein mimicry approaches to elicit broadly neutralizing antibodies for HIV-1
Journal of Biomedical Science,
Год журнала:
2024,
Номер
31(1)
Опубликована: Авг. 21, 2024
Abstract
Human
immunodeficiency
virus
type
1
(HIV-1)
vaccine
immunogens
capable
of
inducing
broadly
neutralizing
antibodies
(bNAbs)
remain
obscure.
HIV-1
evades
immune
responses
through
enormous
diversity
and
hides
its
conserved
vulnerable
epitopes
on
the
envelope
glycoprotein
(Env)
by
displaying
an
extensive
immunodominant
glycan
shield.
In
elite
viremic
controllers,
glycan-dependent
bNAbs
targeting
Env
have
been
isolated
are
utilized
as
design
templates.
However,
immunological
tolerance
mechanisms
limit
development
these
in
general
population.
The
well
characterized
monoclonal
variants
frequently
exhibit
levels
somatic
hypermutation,
a
long
third
heavy
chain
complementary
determining
region,
or
short
light
complementarity
some
poly-reactivity
to
autoantigens.
This
review
elaborates
obstacles
engaging
manipulating
effective
immunogen
describes
alternative
reverse
vaccinology
approach
develop
novel
category
bNAb-epitope-derived
non-cognate
for
design.
Graphical
Язык: Английский