bioRxiv (Cold Spring Harbor Laboratory),
Год журнала:
2024,
Номер
unknown
Опубликована: Ноя. 22, 2024
SUMMARY
Rare
B
cells
can
have
special
pathogen-recognition
features
giving
them
the
potential
to
make
outsized
contributions
protective
immunity.
However,
rare
naive
infrequently
participate
in
immune
responses.
We
investigated
how
germline-targeting
vaccine
antigen
delivery
and
adjuvant
selection
affect
priming
of
exceptionally
BG18-like
HIV
broadly
neutralizing
antibody-precursor
(~1
50
million)
non-human
primates.
Only
escalating
dose
(ED)
immunization
using
saponin
SMNP
elicited
detectable
germinal
centers
(GCs).
All
groups
had
strong
GC
responses,
but
only
ED+SMNP
bolus+SMNP
induced
memory
>50%
animals.
One
group
vaccine-specific
responses
equivalent
ED+SMNP,
were
rarely
detected.
Following
homologous
boosting,
more
frequent
a
bolus
group,
lower
somatic
hypermutation
affinities.
This
outcome
was
inversely
associated
with
post-prime
antibody
titers,
suggesting
feedback
significantly
influence
precursor
cell
Science Translational Medicine,
Год журнала:
2025,
Номер
17(796)
Опубликована: Апрель 30, 2025
Messenger
RNA
(mRNA)
has
emerged
as
a
highly
effective
and
versatile
platform
for
vaccine
delivery.
We
previously
designed
virus-like
particle
(VLP)-forming
env-gag
mRNA
against
human
immunodeficiency
virus-1
(HIV-1)
that
elicited
envelope-specific
neutralizing
antibodies
protection
from
heterologous
simian-human
virus
(SHIV)
infection
in
rhesus
macaques.
Here,
we
introduce
key
technological
advance
to
this
by
inclusion
of
encoding
retroviral
protease
process
Gag
produce
mature
VLPs.
Appropriately
dosed
timed
expression
the
was
achieved
using
full-length
gag-pol
transcript.
Addition
an
HIV-1
resulted
enhanced
titers
envelope
trimer-binding
mouse
model.
Analogous
results
were
obtained
with
hybrid
Gag-based,
VLP-forming
severe
acute
respiratory
syndrome
coronavirus
2
(SARS-CoV-2)
expressing
engineered
spike
protein.
Thus,
can
increase
immunogenicity
vaccines
pathogens.
bioRxiv (Cold Spring Harbor Laboratory),
Год журнала:
2025,
Номер
unknown
Опубликована: Май 4, 2025
Abstract
Transmembrane
glycoproteins
of
enveloped
viruses
are
the
targets
neutralizing
antibodies
and
essential
vaccine
antigens.
mRNA-LNP
technology
allows
in
situ
production
transmembrane
upon
immunization,
but
biophysical
characterization
antigens
vitro
analysis
post-immunization
antibody
responses
typically
rely
on
soluble
proteins.
Here,
we
present
a
methodological
platform
for
assembling
glycoprotein
candidates
into
lipid
nanodiscs.
We
demonstrate
utility
nanodiscs
HIV
membrane
proximal
external
region
(MPER)-targeting
development
by
binding
assays
using
surface
plasmon
resonance
(SPR),
ex
vivo
B
cell
sorting
with
fluorescence-activated
(FACS),
determining
structure
prototypical
MPER-targeting
immunogen
nanodisc
complex
three
broadly
(bnAbs),
including
MPER
bnAb
10E8,
to
3.5
Å
cryogenic
electron
microscopy
(cryo-EM),
providing
template
structure-based
design
MPER.
Overall,
offers
tool
accelerating
next-generation
viral
vaccines.
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.
Microbiological Research,
Год журнала:
2025,
Номер
299, С. 128229 - 128229
Опубликована: Май 21, 2025
Despite
numerous
efforts,
a
successful
vaccine
against
HIV-1
remains
elusive.
An
effective
must
overcome
the
virus's
sophisticated
immune
evasion
strategies
and
induce
production
of
broadly
neutralizing
antibodies
to
counteract
HIV-1's
rapid
mutation,
replication,
transmission
within
between
hosts.
predominantly
evades
recognition
clearance
through
mechanisms
such
as
genomic
mutations,
alterations
in
envelope
protein
affinity,
formation
latent
viral
reservoirs,
interference
with
major
histocompatibility
complex
class
I
antigen
presentation.
Although
considerable
efforts
have
focused
on
generating
potent
vaccines
that
elicit
bnAbs,
probability
achieving
exceedingly
low
given
immune-evasive
tactics.
This
review
discusses
principal
highlights
latest
progress
research,
providing
fresh
perspectives
insights
for
design
vaccines.
Nature Biomedical Engineering,
Год журнала:
2025,
Номер
unknown
Опубликована: Июнь 3, 2025
Understanding
the
mechanistic
interplay
between
antibodies
and
invading
pathogens
is
essential
for
vaccine
development.
Current
methods
are
labour
time
intensive
limited
by
sample
preparation
bottlenecks.
Here
we
present
microfluidic
electron
microscopy-based
polyclonal
epitope
mapping
(mEM),
which
combines
microfluidics
with
single-particle
microscopy
structural
characterization
of
immune
complexes
using
small
volumes
sera
(<4
µl).
First,
used
mEM
to
map
in
from
infected
vaccinated
individuals
against
five
viral
glycoproteins
negative-stain
microscopy.
The
detected
a
greater
number
epitopes
compared
conventional
methods.
Second,
cryo-electron
characterize
two
coronavirus
spikes
one
HA
glycoprotein
without
antibodies.
Finally,
mapped
individual
antibody
responses
over
mice
human
immunodeficiency
virus
envelope
N332-GT5.
enables
rapid,
high-throughput
targeting
broad
range
glycoproteins,
facilitating
better
understanding
infection
guiding
structure-based
design.
bioRxiv (Cold Spring Harbor Laboratory),
Год журнала:
2024,
Номер
unknown
Опубликована: Дек. 9, 2024
Abstract
Antibodies
are
crucial
therapeutics,
comprising
a
significant
portion
of
approved
drugs
due
to
their
safety
and
clinical
efficacy.
Traditional
antibody
discovery
methods
labor-intensive,
limiting
scalability
high-throughput
analysis.
Here,
we
improved
upon
our
streamlined
approach
combining
structural
analysis
bioinformatics
infer
heavy
light
chain
sequences
from
electron
potential
maps
serum-derived
polyclonal
antibodies
(pAbs)
bound
antigens.
Using
ModelAngelo,
an
automated
structure-building
tool,
accelerated
pAb
sequence
determination
identified
matches
in
B
cell
repertoires
via
ModelAngelo
derived
Hidden
Markov
Models
(HMMs)
associated
with
structures.
Benchmarking
against
results
non-human
primate
HIV
vaccine
trial,
pipeline
reduced
time
weeks
under
day
higher
precision.
Validation
murine
immune
sera
influenza
vaccination
revealed
multiple
protective
antibodies.
This
workflow
enhances
discovery,
enabling
faster,
more
accurate
mapping
responses
broad
applications
development
therapeutic
discovery.
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.
