New
strategies
are
needed
to
reduce
the
incidence
of
malaria,
and
promising
approaches
include
development
vaccines
monoclonal
antibodies
(mAbs)
that
target
circumsporozoite
protein
(CSP).
To
select
best
candidates
speed
development,
it
is
essential
standardize
preclinical
assays
measure
potency
such
interventions
in
animal
models.Two
assay
configurations
were
studied
using
transgenic
Plasmodium
berghei
expressing
falciparum
full-length
protein.
The
measured
(1)
reduction
parasite
infection
liver
(liver
burden)
following
an
intravenous
(i.v)
administration
sporozoites
(2)
protection
from
parasitaemia
mosquito
bite
challenge.
Two
human
CSP
mAbs,
AB311
AB317,
compared
for
their
ability
inhibit
infection.
Multiple
independent
experiments
conducted
define
variability
resultant
impact
on
discriminate
differences
mAb
functional
activity.Overall,
produced
highly
consistent
results
all
individual
showed
greater
activity
AB317
as
calculated
by
dose
required
50%
inhibition
(ID50)
well
serum
concentration
(IC50).
data
then
used
model
experimental
designs
with
adequate
statistical
power
rigorously
screen,
compare,
rank
order
novel
anti-CSP
mAbs.The
indicate
vivo
described
here
can
provide
reliable
information
comparing
mAbs.
also
guidance
regarding
selection
appropriate
design,
selection,
group
sizes.
Cell Host & Microbe,
Год журнала:
2018,
Номер
24(1), С. 43 - 56
Опубликована: Июль 1, 2018
The
development
of
highly
effective
and
durable
vaccines
against
the
human
malaria
parasites
Plasmodium
falciparum
P.
vivax
remains
a
key
priority.
Decades
endeavor
have
taught
that
achieving
this
goal
will
be
challenging;
however,
recent
innovation
in
vaccine
research
diverse
pipeline
novel
candidates
for
clinical
assessment
provides
optimism.
With
first-generation
pre-erythrocytic
aiming
licensure
coming
years,
it
is
important
to
reflect
on
how
next-generation
approaches
can
improve
their
success.
Here
we
review
latest
seek
prevent
infection,
disease,
transmission
highlight
some
major
underlying
immunological
molecular
mechanisms
protection.
synthesis
rational
antigen
selection,
immunogen
design,
immunization
strategies
induce
quantitatively
qualitatively
improved
immune
effector
offers
promise
sustained
high-level
Nature Immunology,
Год журнала:
2018,
Номер
19(11), С. 1199 - 1211
Опубликована: Окт. 12, 2018
Development
of
a
malaria
vaccine
remains
critical
priority
to
decrease
clinical
disease
and
mortality
facilitate
eradication.
Accordingly,
RTS,S,
protein-subunit
vaccine,
has
completed
phase
III
trials
confers
~30%
protection
against
infection
over
4
years.
Whole-attenuated-sporozoite
viral-subunit
vaccines
induce
between
20%
100%
controlled
human
infection,
but
there
is
limited
published
evidence
date
for
durable,
high-level
efficacy
(>50%)
natural
exposure.
Importantly,
fundamental
scientific
advances
related
the
potency,
durability,
breadth
location
immune
responses
will
be
required
improving
with
these
other
approaches.
In
this
Review,
we
focus
on
current
understanding
immunological
mechanisms
from
animal
models
studies,
how
data
should
inform
development
next-generation
vaccines.
Furthermore,
introduce
concept
using
passive
immunization
monoclonal
antibodies
as
new
approach
prevent
eliminate
malaria.
Nature Communications,
Год журнала:
2019,
Номер
10(1)
Опубликована: Май 15, 2019
RTS,S/AS01E
has
been
tested
in
a
phase
3
malaria
vaccine
study
with
partial
efficacy
African
children
and
infants.
In
cohort
of
1028
subjects
from
one
low
(Bagomoyo)
two
high
(Nanoro,
Kintampo)
transmission
sites,
we
analysed
IgG
plasma/serum
concentration
avidity
to
CSP
(NANP-repeat
C-terminal
domains)
after
3-dose
vaccination
against
time
clinical
events
during
12-months.
Here
report
that
induces
substantial
increases
levels
pre-
post-vaccination
(p
<
0.001),
higher
NANP
than
C-terminus
(2855
vs
1297
proportional
change
between
means),
concentrations
avidities
infants
0.001).
Baseline
are
elevated
cases
controls
Both,
magnitude
(hazard
ratio
[95%
confidence
interval]
0.61
[0.48-0.76])
(0.07
[0.05-0.90])
significantly
associated
efficacy.
the
emerges
as
significant
contributor
RTS,S/AS01E-mediated
protection.
Frontiers in Immunology,
Год журнала:
2023,
Номер
13
Опубликована: Янв. 4, 2023
Malaria
is
a
global
infectious
disease
that
remains
leading
cause
of
morbidity
and
mortality
in
the
developing
world.
Multiple
environmental
host
parasite
factors
govern
clinical
outcomes
malaria.
The
immune
response
against
Plasmodium
heterogenous
stage-specific
both
human
mosquito
vector.
virulence
predominantly
associated
with
its
ability
to
evade
host’s
response.
Despite
availability
drug-based
therapies,
parasites
can
acquire
drug
resistance
due
high
antigenic
variations
allelic
polymorphisms.
lack
licensed
vaccines
infection
necessitates
development
effective,
safe
successful
therapeutics.
To
design
an
effective
vaccine,
it
important
study
evasion
strategies
proteins,
which
are
targets
This
review
provides
overview
defense
mechanisms
during
infection.
Furthermore,
we
also
summarize
discuss
current
progress
various
anti-malarial
vaccine
approaches,
along
antibody-based
therapy
involving
monoclonal
antibodies,
research
advancements
host-directed
therapy,
together
open
new
avenues
for
novel
immunotherapies
malaria
transmission.
