SERCEB: what is it What opportunities for collaboration

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SERCEB what is it? What opportunities for
collaboration

• 7/2006

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Overview

• One of 10 regional centers of excellence (RCEs)
  in biodefense and emerging infections-one for
  each Soc Security region.
• Charge is to discover and develop vaccines,
  drugs, diagnostics that will help protect the
  nation
• Now in year 4 of 6 anticipate renewal submission
  in 12-15 months

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SERCEB?

• SE Regional Center of Excellence in Biodefense
• Administratively housed at Duke
• Charter members include Duke, UNC, Emory,
  UAB/SRI, Vanderbilt, U FL (each members of
  steering committee)
• Affiliates include virtually every other research
  university in the SE

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SERCEB leadership

• Initially (3/1/2003) Bart Haynes at Duke he also
  received huge CHAVI grant in 2005, requiring 100
  effort on HIV vaccine development
• 11/05 switched to Fred Sparling (UNC) who took
  faculty position at Duke, keeping grant at Duke
• An example of inter-institutional sharing and
  collaboration-but not a sign of for whom one
  roots in basketball

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Why RCEs?

• Presidents decision, with push from Congress
  response to anthrax attack of 10/2001 and twin
  towers/Pentagon attacks of 9/11/2001
• At present, only a modest part of the entire
  spectrum of biodefense funding by NIH and an even
  smaller part of the total federal funding for
  same (DARPA, DOD, HHS, CDC, other)

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NIAID funding for biodefense

• About 1.6 B/year, equal to HIV funding and the
  aggregate of everything else outside of HIV and
  BD (ie about 1/3 of NIAID budget)
• Of this, about 100M/year for the RCEs about
  10M/year for SERCEB
• Other big ticket items RBLs (regional BSL-2/3
  labs, and NBLs (2 national BSL-3/4 labs) Duke is
  completing an RBL

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Focus on Category A select agents

• For SERCEB, this translates into
• Pox viruses improved vaccines, novel drugs
• Anthrax sporulation as a target for drug
  discovery
• Tularemia pathogenesis and immunology
• Y pestis (wrapped up at year 3)
• Applied and basic immunology

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Pox virus vaccines

• 3 projects
• D Garber (Emory)-modified MVA, deleted of immune
  suppression genes, addition of cytokines to
  enhance response
• D Pickup/Bob Johnston (Duke and UNC)-VEE VRPs as
  delivery platform for select pox antigens
  effects of pox immune response accessory genes in
  VRP platform

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Additional project vector comparison trial

• Pox B5R antigen in adenovirus, VRP, DNA, MVA,
  VSV, Mtb vectors, in variable prime boost
  strategies, in mice and NHPs primary goal is to
  determine relative immunogenicity secondary goal
  of possible partial protection from vaccinia
  challenge (Liz Ramsberg, Duke, et al)

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Pox drug Discovery

• Combined rational discovery based on determined
  crystal structures of Pox enzymes (3 determined
  to date at UAB) combined with relatively high
  throughput screens of existing libraries at
  SRI/UAB
• Industry collaborations HDP cidofovir, Gleevec).
  Gleevec kinase inhibitors inhibit pox spread
  between cells (D Kalman at Emory R Moyer at UFL)

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Pox receptor discovery

• Mabs against Hela cells block attachment
• Cloned pox proteins mediate attachment
• Risky project aimed at long term drug discovery
  or vaccine antigens (R Moyer at UFL and others at
  Emory and Vanderbilt)

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Pox programs still worthwhile?

• Two purchased vaccines and a 3rd-MVA-in the late
  stages of development
• External review at Emory of vaccine program 4/06
  focus on improved MVA and basic science
• External review of receptor program tomorrow at
  Vanderbilt

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Plague program

• Focus on outer membrane proteins and also the
  Yersinia pestis iron scavenging systems as either
  vaccine targets, or (iron systems) as druggable
  targets (Sue Straley and Bob Perry, UKY)
• Ended at end of year 3, slow progress, also
  initial peer review limited funds to 3 years

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Anthrax spores as targets

• Translation of B subtilis spore genetics into B
  anthracis spore genes as keys to pathogenesis
  and as targets for drug screens (Phil Hanna,
  UMich Charley Moran, Emory)
• Serendipity discovery of a wash solution that
  facilitates cleanup of spores by promoting
  exsporulation

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Basic immunology-focus on innate immunity

• Role of intracellular signalling and pattern
  recognition genes (eg, Nod or Caterpillar genes)
  in control of relevant infections possible drug
  development targets (J. Ting, UNC)
• Dendritic cells as targets for enhanced antigen
  delivery (B Pulendran, Emory)
• T regs as targets for improved vaccines (G
  Sempowski, Duke)

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Collaborations and Innovations

• B Pulendran and also D Compans (Emory) and
  colleagues at G Tech use of nanoparticles or
  other nanotech for improved vaccine delivery
  (Compans) or antigen delivery (Pulendran).
  Exciting results are a result of a 10 year
  inter-institutional agreement

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Better memory responses to vaccines?

• Different strategies (vectors, adjuvants) to
  enhance B cell memory responses ( Rafi Ahmed,
  Emory)

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Other programs

• Developmental projects 5-9 yearly grants,
  internally reviewed but approved by NIH, each for
  50-100K for each of 2 years
• Career development sabbaticals for faculty,
  senior post docs in biodefense arena, either
  basic or clinical emphasis. Minority recruitment?

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F tularensis program

• Development of genetic system for Ft creation of
  mutants specifically altered in ability to cause
  airborne infection (T Kawula, UNC)
• Mapping of key epitopes (J Frelinger, UNC)
• Both result of developmental projects

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Other developmental projects

• Humanized mouse for immune response, pathogenesis
  ( L Su, UNC)
• Proteomics for Ft detection (C Borchers, UNC)
• Marburg genetics (R Baric, UNC)
• Novel drugs for Y pestis ( M Oliveira, U KY) or B
  anthracis (A Clairborne, Wake Forest)

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Other new projects new Opportunities funds

• Each year a pot of funds are put up by NIH to
  facilitate either
• trans-RCE projects (eg, HTS facility based at
  Harvard, for all RCEs),
• or new local RCE projects (eg, supplements to
  existing cores, or new programs such as the RMSF
  genetic vaccine (SERCEB and SW RCE)

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Cores

• Within SERCEB
• Mabs, mouse and human
• Protein expression
• Structural biology
• Drug screening
• Computational biology
• Immune monitoring
• Ethics policy and law

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Where does industry fit in?

• We are under pressure to develop as well as
  discover
• Ambiguity reigns-do we have enough money to
  really develop a drug? Will pharma jump in?
• At present, NIH expects us to get some products
  into phase 1 but do not expect us to be able to
  support phase 3 trials

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Can we share across boundaries?

• Yes-a spirit of collaboration that is
  unprecedented exists
• No still some problems with MTAs and IP
• A new product development council is being
  activated to review and guide products that are
  emerging-15 members with industry experience,
  most in biotech, meets 8/1/2006

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SERCEB products?

• Outside of some Mabs (anti EBOLA, anti-anthrax
  LT) and possibly some diagnostics (metabolomics,
  Abs on a chip, proteomics) we are not close yet.
  Hopefully, pox programs will yield something
  pretty soon-but do we really need these?

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Future of the RCEs?

• Depends on NIH and ultimately congress
• And also on whether there is another BT type
  attack
• May morph into centers for BD and EMERGING
  INFECTIONS