Journal of Clinical Investigation,
Journal Year:
2025,
Volume and Issue:
135(6)
Published: March 16, 2025
Approximately
one-quarter
of
the
global
population
is
estimated
to
be
infected
with
Mycobacterium
tuberculosis.
New
developments
in
vaccine
design
and
therapeutics
are
urgently
needed,
particularly
face
multidrug-resistant
tuberculosis
(TB).
In
this
issue
JCI,
Sakai
colleagues
used
a
multidisciplinary
approach
determine
that
trehalose-6-monomycolate
(TMM),
mycobacterial
cell
wall
lipid,
serves
as
T
antigen
presented
by
CD1b.
CD1b-TMM–specific
cells
were
characterized
conserved
receptor
features
present
at
elevated
frequencies
individuals
active
TB
disease.
These
findings
highlight
dual
role
TMM
stimulating
both
innate
adaptive
immunity
broaden
our
understanding
CD1-mediated
lipid
recognition
unconventional
cells.
Science Advances,
Journal Year:
2025,
Volume and Issue:
11(1)
Published: Jan. 1, 2025
Intradermal
Bacillus
Calmette-Guérin
(BCG)
is
the
most
widely
administered
vaccine,
but
it
does
not
sufficiently
protect
adults
against
pulmonary
tuberculosis.
Recent
studies
in
nonhuman
primates
show
that
intravenous
BCG
administration
offers
superior
protection
Mycobacterium
tuberculosis
(
Mtb
).
We
used
single-cell
analysis
of
bronchoalveolar
lavage
cells
from
rhesus
macaques
vaccinated
via
different
routes
and
doses
to
identify
alterations
immune
ecosystem
airway
following
vaccination.
Our
findings
reveal
high-dose
induces
an
influx
polyfunctional
T
macrophages
airways,
with
alveolar
displaying
a
basal
activation
state
absence
purified
protein
derivative
stimulation,
defined
part
by
interferon
signaling.
Enhanced
intercellular
signaling
stronger
helper
1–T
17
transcriptional
responses
were
observed
stimulation.
These
results
suggest
vaccination
creates
specialized
environment
primes
for
effective
clearance.
The Journal of Experimental Medicine,
Journal Year:
2025,
Volume and Issue:
222(4)
Published: Jan. 17, 2025
Tuberculosis
(TB)
is
a
major
health
burden
worldwide
despite
widespread
intradermal
(ID)
BCG
vaccination
in
newborns.
We
previously
demonstrated
that
changing
the
route
and
dose
from
5
×
105
CFUs
ID
to
107
i.v.
resulted
prevention
of
Mycobacterium
tuberculosis
(Mtb)
infection
TB
disease
highly
susceptible
nonhuman
primates.
Identifying
immune
mechanisms
protection
following
will
facilitate
development
more
effective
vaccines
against
TB.
Here,
we
depleted
lymphocyte
subsets
prior
during
Mtb
challenge
BCG-vaccinated
macaques
identify
those
necessary
for
protection.
Depletion
adaptive
CD4
T
cells,
but
not
CD8αβ
loss
with
increased
burdens
dissemination,
indicating
cells
are
critical
BCG-mediated
unconventional
CD8α-expressing
lymphocytes
(NK
innate
CD4+CD8α+
double-positive
cells)
abrogated
most
BCG-immunized
macaques,
supporting
further
investigation
into
which
these
cell
contribute
after
vaccination.
npj Vaccines,
Journal Year:
2023,
Volume and Issue:
8(1)
Published: Oct. 13, 2023
Abstract
Breakthrough
findings
in
the
clinical
and
preclinical
development
of
tuberculosis
(TB)
vaccines
have
galvanized
field
suggest,
for
first
time
since
bacille
Calmette-Guérin
(BCG),
that
a
novel
protective
TB
vaccine
is
on
horizon.
Here
we
highlight
are
pipeline
review
basis
optimism
both
space.
We
describe
immune
signatures
could
act
as
immunological
correlates
protection
(CoP)
to
facilitate
comparison
vaccines.
Finally,
discuss
new
animal
models
expected
more
faithfully
model
pathology
complex
responses
observed
human
populations.
Nature Microbiology,
Journal Year:
2023,
Volume and Issue:
8(11), P. 2080 - 2092
Published: Oct. 9, 2023
Abstract
Tuberculosis,
caused
by
Mycobacterium
tuberculosis
(Mtb),
is
the
most
common
cause
of
death
in
people
living
with
human
immunodeficiency
virus
(HIV).
Intra-dermal
Bacille
Calmette–Guérin
(BCG)
delivery
only
licensed
vaccine
against
tuberculosis;
however,
it
offers
little
protection
from
pulmonary
adults
and
contraindicated
HIV.
Intravenous
BCG
confers
Mtb
infection
rhesus
macaques;
we
hypothesized
that
might
prevent
simian
(SIV)-infected
macaques,
a
model
for
HIV
infection.
Here
intravenous
BCG-elicited
robust
airway
T
cell
influx
elevated
plasma
antibody
titres
both
SIV-infected
naive
animals.
Following
challenge,
all
7
vaccinated
SIV-naive
9
out
12
animals
were
protected,
without
any
culturable
bacteria
detected
tissues.
Peripheral
blood
mononuclear
responses
post-challenge
indicated
early
clearance
animals,
regardless
SIV
These
data
support
immunogenic
efficacious
Nature Immunology,
Journal Year:
2024,
Volume and Issue:
25(8), P. 1411 - 1421
Published: July 12, 2024
Abstract
A
subset
of
individuals
exposed
to
Mycobacterium
tuberculosis
(
Mtb
)
that
we
refer
as
‘resisters’
(RSTR)
show
evidence
IFN-γ
−
T
cell
responses
-specific
antigens
despite
serially
negative
results
on
clinical
testing.
Here
found
cells
in
RSTR
were
clonally
expanded,
confirming
the
priming
adaptive
immune
following
exposure.
CD4
+
showed
enrichment
H
17
and
regulatory
cell-like
functional
programs
compared
from
with
latent
infection.
Using
public
datasets,
these
associated
lack
progression
active
among
South
African
adolescents
infection
bacterial
control
nonhuman
primates.
Our
findings
suggested
may
successfully
exposure
established
a
set
biomarkers
facilitate
further
study
this
phenotype.
npj Vaccines,
Journal Year:
2024,
Volume and Issue:
9(1)
Published: Oct. 30, 2024
The
absence
of
validated
correlates
protection
(CoPs)
hampers
the
rational
design
and
clinical
development
new
tuberculosis
vaccines.
In
this
review,
we
provide
an
overview
potential
CoPs
in
vaccine
research.
Major
hindrances
opportunities
are
then
discussed.
Based
on
recent
progress,
it
is
reasonable
to
anticipate
that
success
ongoing
efforts
identify
would
be
a
game-changer
development.
