March 2019 digital v1

IDRI’S TB VACCINE ENTERS PHASE 2 TRIALS
An experimental vaccine, called
ID93, developed by scientists at the
Infectious Disease Research Institute
(IDRI) in Seattle, has advanced to phase
2 clinical testing.
The TB vaccine candidate combines
ID93, a fusion of 4 mycobacterium
tuberculosis antigens with diverse roles
in pathogenesis, with the adjuvant
GLA-SE, a synthetic toll-like receptor
4 (TLR4) agonist, formulated in a
squalene oil and water nano-emulsion
that has a significant safety track
record.
“The four antigens representing
different families of mycobacterium
tuberculosis (MTB) proteins have
been shown to be recognised in
MTB-exposed individuals. RV1813 is a
conserved hypothetical protein that
is upregulated under hypoxic growth
and predicted to be localised in the
outer membrane. RV2608 (PPE42) is a
probable outer membrane-associated
PPE (pro-pro-glu motif-containing)
protein. RV3619 (ESXV) and RV3620
(ESXW) are secreted proteins belonging
to the ESAT-6 family of virulence
factors,» says Rhea Coler, Senior. Vice
President, Preclinical & Translational
Science at IDRI.
Explaining the role of the adjuvant,
Rhea Coler
STUDIES HAVE SHOWN
THAT ID93+GLA-SE
IS EFFICACIOUS
PROPHYLACTICALLY
AS WELL AS
THERAPEUTICALLY
Coler said, GLA-SE skews the immune
response to a TH1 type immune
response with induction of CD4+ T
cells. Human immune correlates of
protection against TB have not yet
been identified. T-helper 1 (TH1) type
cellular immunity is known to be crucial
for controlling MTB infection and thus
vaccine strategies aim to elicit these
subsets.
Recently, studies have shown
evidence that antibodies may also
contribute to controlling disease in
latently infected individuals.
Pre-clinical studies using mice,
guinea pigs and non-human primates,
have shown that ID93+GLA-SE is
efficacious prophylactically as well as
therapeutically. The vaccine significantly
improved TB treatment outcomes
over antibiotics alone and allowed the
duration of antibiotic treatment to be
reduced by 30%.
Therapeutic efficacy of ID93+GLA-
SE is associated with enhanced TH1
responses, improved MTB clearance,
and reduced pulmonary inflammation.
“In mice and humans, we have
observed immune responses 6-12
months after immunization,’’ Coler
adds.
As a part of the efforts to make
the vaccine affordable for those who
need it, IDRI is planning to transfer the
technology involved in the production
of the vaccine to 3 different facilities in
Africa and Asia.
TB a big challenge.
TB kills more than 1,400 people every day, or around
480,000 Indians every year, as per official estimates.
India accounts for nearly 10% of the global burden of HIVassociated
TB. According to the India TB Report 2018, 87,000
HIV-associated TB patients are being diagnosed annually. HIV
prevalence among incident TB patients is estimated to be
4%. The mortality in TB/HIV co-infected patients is very high
and 12,000 people die every year from this condition.
Prevention as centrepiece?
Alongside free diagnosis and treatment, the NSP provides
an incentive for nutritional support. “In India, undernutrition
is a driver of TB,” comments Dr Sameer. Undernutrition and
TB have a bidirectional relationship. While undernutrition
increases the risk of TB, contracting the disease increases
the risk of malnutrition, thereby culminating in an intercausal
cycle for the two diseases.
India has practically doubled the budget to meet the
target of eliminating TB by 2025. “The government has
backed the NSP with a historic resource commitment of Rs
12,000 crores over three years, while it increased investment
in research and development to $6 million,” comments Dr
Sameer.
Some experts are of the opinion that the current budget
allocation may still be way below the actual requirement.
Considering the enormity and the urgency of the situation,
both the regular, drug-susceptible TB as well as the drugresistant
TB need additional expenditure.
In order to achieve the target of ending TB by 2025, India
needs to reduce new TB cases by 10 percent every year. But
recent reports indicate that the country is nowhere near the
number. Moreover, India needs to pay more attention to a
preventive strategy. The goals can’t be translated to reality
until prevention becomes the centrepiece of India’s TB policy,
warn experts.
28 / FUTURE MEDICINE / March 2019