Novel Approaches to TB Vaccine Development

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Novel Approaches to TB Vaccine Development

• Stop TB Partners Forum
• March 24, 2009
• Rio de Janeiro, Brazil
• Jerald C. Sadoff, MD
• Aeras Global TB Vaccine Foundation

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Potential of a New TB Vaccine

• Eliminate TB as a global public health threat, in
  line with global targets (lt1 case/million)
• In conjunction with new drugs and diagnostics
• Vaccines can prevent onset and reduce
  transmission of disease
• TB will not be eliminated without a new TB
  vaccine
• Safe and effective in preventing TB in children,
  adolescents and adults, including people with HIV
• Protect against all forms of TB including MDR
  and XDR
• Reduce the cost and burden of TB related medical
  care on health care systems and patients

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Block Initial Infection
Prevent Latent Infection
Prevent Early Disease
Prevent Reactivation Disease
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TB Vaccine Pipeline
Pre-clinical
Phase II
Phase IIB
Phase I
Phase III
AERAS427
VPM 1002
M. Vaccae
Other rBCG rMtb
Recombinant BCGs for priming infants
AERAS 402/ Crucell (2009)
Replication-deficient viral vectored vaccines for
boosting infants, young adults HIV positive
AERAS405 Capsid
AERASOther Virus
MVA85A/ AERAS 485 (2009)
GSK M72
HyVac4/ AERAS 404
Other Protein PSS
Recombinant fusion proteins for boosting infants,
adolescents, young adults, HIV positive
Hybrid 1 SSI
AERASPSS
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Novel Approaches Recombinant BCG (rBCG) - a
Better BCG

• Safer
• Incorporates escape from the endosome where it
  hides
• Safer in HIV infected infants or others with
  immune-suppression
• May eliminate need for HIV screening of infants
  prior to rBCG
• More immunogenic
• BCG or rBCG boosted with another TB vaccine
  (either viral vector or protein adjuvant) is
  much better than either vaccine alone
• Highest vaccine induced immunogenicity in animals
  humans ever seen
• Best protection in NHP against TB challenge
• Constructed to over-express antigens from each
  stage of the TB life cycle utilizing unique
  molecular biology tools
• Prevent infection and reactivation utilizing
  prime-boost regimens
• A new vaccine candidate (AERAS-427) with all of
  these properties is expected to enter the clinic
  in 2009

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BCG Immunized Adults St Louis
PRELIMINARY DATA 10 DEC 2008
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Novel ApproachesAerosol Delivery of New TB
Vaccines

• Very small particles (2-4 microns) get deep into
  the lung
• Two methods of creating and delivering these
  particles are being developed
• Nebulizer with laser drilled filter for liquid
  vaccines
• Spray drying that yields dry powder particles
  delivered by a low-cost plastic inhaler
• Preclinical testing in NHPs showed very high
  levels of vaccine-induced cellular immunity
  against TB in the lung following aerosol
  immunization
• Liquid and powder methods are being applied to
  viral-vector (AERAS-402) and nucleocapsid
  (AERAS-405) vaccine candidates
• Aerosol delivery may provide an easy, affordable
  delivery mechanism that could eliminate the need
  for needles and cold chain and provide superior
  protection

Spray Drying
Purified nucleocapsid
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Novel Approaches to Manufacturing

• Building manufacturing capacity and partnerships
  now to
• Reduce the cost and time to manufacture and
  deliver vaccines to all who need them through
  novel fermentation process
• Produce enough bulk doses of rBCG (200
  million/year) and nucleocapsids (gt1 billion/year)
  to meet the worlds estimated need
• Work with partners in emerging economies such as
  India, China, Brazil and South Africa to produce,
  fill, finish and distribute vaccines at the
  lowest possible price
• Ensure uniformity of quality
• Minimize lag time between licensure and
  distribution

Fermentation Tanks Aeras Manufacturing
Facility Rockville MD USA
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Help Make TB RD a Global Priority

• New TB tools vaccines, drugs and diagnostics -
  will help achieve global development goals and
  are critical to controlling the TB pandemic
• Researchers around the world are working on new
  and innovative approaches to develop and deliver
  new tools
• New tools need to be a global priority to help
  ensure rapid development and distribution
• Help make TB RD a Global Priority by
• Including development of new TB vaccines, drugs
  and diagnostics in overall advocacy efforts
• Building endemic country support for new TB tools
• Advocating for donor country financial support
  for TB RD
• Encouraging private sector investment in new
  tools for TB