Immunological Reviews,
Journal Year:
2019,
Volume and Issue:
293(1), P. 190 - 215
Published: Dec. 16, 2019
Summary
The
efficient
spread
of
malaria
from
infected
humans
to
mosquitoes
is
a
major
challenge
for
elimination
initiatives.
Gametocytes
are
the
only
Plasmodium
life
stage
infectious
mosquitoes.
Here,
we
summarize
evidence
naturally
acquired
anti‐gametocyte
immunity
and
current
state
transmission
blocking
vaccines
(TBV).
Although
gametocytes
intra‐erythrocytic
when
present
in
humans,
developing
falciparum
may
express
proteins
on
surface
red
blood
cells
that
elicit
immune
responses
exposed
individuals.
This
response
reduce
burden
circulating
gametocytes.
For
both
P.
vivax
,
there
solid
antibodies
against
antigens
gametocyte
surface,
co‐ingested
with
gametocytes,
can
influence
Transmission
reducing
immunity,
infection
mosquitoes,
well‐acknowledged
but
poorly
quantified
phenomenon
forms
basis
development
TBV.
enhancing
increasing
likelihood
or
intensity
more
speculative
nature
convincingly
demonstrated
.
With
increased
interest
elimination,
TBV
monoclonal
have
moved
center
vaccine
development.
Methodologies
prioritize
evaluate
products
urgently
needed.
Microorganisms,
Journal Year:
2019,
Volume and Issue:
7(6), P. 179 - 179
Published: June 21, 2019
Malaria
is
a
severe
disease
caused
by
parasites
of
the
genus
Plasmodium,
which
transmitted
to
humans
bite
an
infected
female
mosquito
species
Anopheles.
remains
leading
cause
mortality
around
world,
and
early
diagnosis
fast-acting
treatment
prevent
unwanted
outcomes.
It
most
common
in
Africa
some
countries
Asia,
while
developed
world
malaria
occurs
as
imported
from
endemic
areas.
The
sweet
sagewort
plant
was
used
second
century
BC
treat
fever
China.
Much
later,
quinine
started
being
antimalaria
drug.
A
global
battle
against
1955,
Croatia
declared
1964
be
year
eradication
malaria.
World
Health
Organization
carries
out
control
program
on
scale,
focusing
local
strengthening
primary
health
care,
disease,
timely
treatment,
prevention.
Globally,
burden
lower
than
ten
years
ago.
However,
last
few
years,
there
has
been
increase
number
cases
world.
moving
towards
targets
established
WHO,
but
that
progress
slowed
down.
Immunity,
Journal Year:
2018,
Volume and Issue:
48(5), P. 855 - 871
Published: May 1, 2018
HIV-1
vaccine
development
has
been
stymied
by
an
inability
to
induce
broadly
reactive
neutralizing
antibodies
the
envelope
(Env)
trimer,
sole
viral
antigen
on
virion
surface.
Antibodies
isolated
from
HIV-1-infected
donors,
however,
have
shown
recognize
all
major
exposed
regions
of
prefusion-closed
Env
and
emerging
understanding
immunological
structural
characteristics
these
epitopes
they
is
enabling
new
approaches
design.
Antibody
lineage-based
design
creates
immunogens
that
activate
naive
ancestor-B
cell
a
target
antibody
lineage
mature
intermediate-B
cells
toward
effective
neutralization,
with
proof
principle
achieved
select
HIV-1-neutralizing
lineages
in
human-gene
knock-in
mouse
models.
Epitope-based
involves
engineering
sites
vulnerability
as
defined
recognition
antibodies,
cross-reactive
elicited
animal
Both
epitope-based
are
being
readied
for
human
clinical
trials.
Cell Host & Microbe,
Journal Year:
2018,
Volume and Issue:
24(1), P. 43 - 56
Published: July 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
Science,
Journal Year:
2019,
Volume and Issue:
366(6470)
Published: Oct. 31, 2019
Engineering
better
bnAbs
A
highly
effective
HIV
vaccine
has
been
the
goal
of
vaccinologists
for
nearly
35
years.
successful
would
need
to
induce
broadly
neutralizing
antibodies
(bnAbs)
that
are
capable
multiple
strains
(see
Perspective
by
Agazio
and
Torres).
Steichen
et
al.
report
a
strategy
in
which
first
shot
can
lead
immune
responses
generate
desired
bnAbs.
By
combining
knowledge
human
antibody
repertoires
structure
guide
design,
they
validated
candidate
immunogens
through
functional
preclinical
testing.
Saunders
designed
with
differences
binding
strength
bnAb
precursors,
enabled
selection
rare
mutations
after
immunization.
The
promoted
precursor
maturation
humanized
mice
macaques.
Science
,
this
issue
p.
eaax4380
eaay7199
;
see
also
1197
Journal of Clinical Investigation,
Journal Year:
2022,
Volume and Issue:
132(1)
Published: Jan. 3, 2022
The
long
road
to
vaccine
developmentAfter
more
than
four
decades
of
basic
research
and
clinical
trials,
the
World
Health
Organization
(WHO)
has
recommended
malaria
RTS,S
for
widespread
use
among
children
living
in
endemic
areas.Pioneering
studies
using
rodent
models
directed
by
Ruth
S.
Nussenzweig
at
New
York
University
School
Medicine
demonstrated
late
1960s
that
immunization
with
attenuated
sporozoites
-the
infective
stage
Plasmodium
-induces
immune
responses
protect
against
parasite
infection
(1).These
also
identified
circumsporozoite
protein
(CSP),
sporozoite-specific
molecule
recognized
protective
is
antigen
incorporated
(2).The
CSP
expressed
on
surface
different
species
contains
a
central
domain
tandem
repeats
represent
approximately
30%
entire
sequence.Extensive
experimental
evidence
indicates
binding
antibodies
these
immobilizes
sporozoites,
preventing
hepatocytes,
an
obligatory
this
(Figure
1).The
hepatitis
B
virus-like
particle
genetically
fused
portion
repeat
C-terminal
region
P.
falciparum
(3).
New England Journal of Medicine,
Journal Year:
2022,
Volume and Issue:
387(5), P. 397 - 407
Published: Aug. 3, 2022
New
approaches
for
the
prevention
and
elimination
of
malaria,
a
leading
cause
illness
death
among
infants
young
children
globally,
are
needed.We
conducted
phase
1
clinical
trial
to
assess
safety
pharmacokinetics
L9LS,
next-generation
antimalarial
monoclonal
antibody,
its
protective
efficacy
against
controlled
human
malaria
infection
in
healthy
adults
who
had
never
or
received
vaccine
malaria.
The
participants
L9LS
either
intravenously
subcutaneously
at
dose
mg,
5
20
mg
per
kilogram
body
weight.
Within
2
6
weeks
after
administration
both
control
underwent
which
they
were
exposed
mosquitoes
carrying
Plasmodium
falciparum
(3D7
strain).No
concerns
identified.
an
estimated
half-life
56
days,
it
linearity,
with
highest
mean
(±SD)
maximum
serum
concentration
(Cmax)
914.2±146.5
μg
milliliter
observed
lowest
Cmax
41.5±4.7
those
intravenously;
was
164.8±31.1
68.9±22.3
subcutaneously.
A
total
17
recipients
infection.
Of
single
15
(88%)
protected
Parasitemia
did
not
develop
any
intravenous
L9LS.
developed
intravenously,
subcutaneously,
all
through
21
days
Protection
conferred
by
seen
concentrations
as
low
9.2
milliliter.In
this
small
trial,
administered
infection,
without
evident
concerns.
(Funded
National
Institute
Allergy
Infectious
Diseases;
VRC
614
ClinicalTrials.gov
number,
NCT05019729.).
New England Journal of Medicine,
Journal Year:
2022,
Volume and Issue:
387(20), P. 1833 - 1842
Published: Nov. 1, 2022
CIS43LS
is
a
monoclonal
antibody
that
was
shown
to
protect
against
controlled
Plasmodium
falciparum
infection
in
phase
1
clinical
trial.
Whether
can
prevent
P.
region
which
the
endemic
unknown.We
conducted
2
trial
assess
safety
and
efficacy
of
single
intravenous
infusion
healthy
adults
Mali
over
6-month
malaria
season.
In
Part
A,
assessed
at
three
escalating
dose
levels.
B,
participants
were
randomly
assigned
(in
1:1:1
ratio)
receive
10
mg
per
kilogram
body
weight,
40
kilogram,
or
placebo.
The
primary
end
point,
time-to-event
analysis,
first
detected
on
blood-smear
examination,
performed
least
every
weeks
for
24
weeks.
At
enrollment,
all
received
artemether-lumefantrine
clear
possible
infection.In
330
underwent
randomization;
110
each
group.
risk
moderate
headache
3.3
times
as
high
with
infections
examination
39
(35.5%)
who
20
(18.2%)
86
(78.2%)
6
months,
compared
placebo
88.2%
(adjusted
95%
confidence
interval
[CI],
79.3
93.3;
P<0.001),
75.0%
CI,
61.0
84.0;
P<0.001).CIS43LS
protective
season
without
evident
concerns.
(Funded
by
National
Institute
Allergy
Infectious
Diseases;
ClinicalTrials.gov
number,
NCT04329104.).