SECTION OF RETROVIRAL PATHOGENESIS

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LABORATORY OF RETROVIRUS RESEARCHLAB STRUCTURE

• SECTION OF RETROVIRAL PATHOGENESIS
• Hana Golding, Ph.D. (PI, Lab Chief)
• Keith Peden, Ph.D. (PI)
• Marina Zaitseva, Ph.D. (Senior Staff Fellow)
• SECTION OF RETROVIRAL IMMUNOLOGY
• Dennis Klinman, MD, Ph.D. (PI)
• SECTION OF MOLECULAR RETROVIROLOGY
• Arifa Khan, Ph.D. (PI)

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LABORATORY OF RETROVIRUS RESEARCHREGULATORY
MISSION (I)

• Review of HIV vaccines (pre-IND, original IND
  submissions, IND amendments, pre-BLA, BLA)
• Provide expert opinions to other CBER
  Laboratories and Divisions on
• Novel Cell Substrates
• Adventitious agents detection
• Retrovirus contamination
• Lentivirus vectors
• Plasmid DNA vaccines
• CpG oligonucleotides and other adjuvants

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LABORATORY OF RETROVIRUS RESEARCHREGULATORY
MISSION (II)

• Presentations to CBER Advisory Committees
• Presentations to the World Health Organization
  and to other international regulatory authorities
• Participation in Interagency Working Groups
• Organization and/or participation in special
  workshops on HIV vaccines, plasmid DNA vaccines,
  and novel cell substrates

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LABORATORY OF RETROVIRUS RESEARCHREGULATORY
MISSION (III)

• Preparation of Guidance Documents for sponsors
  of new vaccines
• Considerations for plasmid DNA vaccines for
  infectious disease indications (Klinman)
• Characterization and qualification of cell
  substrates and other biological starting
  materials for the production of viral vaccines
  (Peden, Khan)
• Preclinical toxicity assessments of preventive
  vaccines to support phase 1 clinical trials
  (Golding)

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SECTION OF RETROVIRAL IMMUNOLOGY Dennis Klinman
(PI)

• Monitor the Safety and Immunomodulatory Activity
  of
• DNA-based Products
• DNA-based products regulated by the FDA
• DNA vaccines
• Synthetic oligodeoxynucleotides (ODN) for
  therapy, immune modulation, adjuvants
• Regulated products in which DNA exists as a
  contaminant
• Proteins produced in bacteria containing
  bacterial DNA.
• Vaccines produced in mammalian cell lines
  containing mammalian DNA.

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Dennis Klinman Accomplishments

• Discovered and patented a new class of
  stimulatory CpG ODN.
• vaccine adjuvants
• immunoprotective agents
• anti-allergens.
• Discovered and patented a new class of
  suppressive ODN.
• for prevention or treatment of autoimmune and
  inflammatory diseases.
• mechanism of action of these ODN.

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SECTION OF RETROVIRAL PATHOGENESIS Hana Golding
(PI)

• STUDIES ON HIV CELL ENTRY
• HIV coreceptor expression and function in primary
  human cells
• new entry inhibitors targeting the HIV coreceptor
  CCR5
• HIV VACCINE TRIALS
• new HIV EIA for differential diagnosis of HIV
  infections in the presence of vaccine-generated
  antibodies
• COUNTER TERRORISM PREPAREDNESS
• new in vitro assays and animal models for
  evaluation of smallpox vaccines potency and
  safety.

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Hana Golding Accomplishments

• HIV-SELECTEST
• Uninfected vaccine trial participants score
  negative, while all HIV infections are diagnosed
  early
• Simple and economical test. Can be implemented in
  sites of future HIV vaccine trials and in blood
  collection centers around the globe.
• SMALLPOX VACCINE EVALUATION
• Reporter-gene based vaccinia neutralization assay
  (high throughput)
• Collaborative work on monkeypox primate challenge
  for 2-animal rule
• Mouse models for tracking vaccinia dissemination
  vaccine safety and post-exposure prophylaxis

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SECTION OF RETROVIRAL PATHOGENESISMarina
Zaitseva (Senior Staff Fellow) Accomplishments

• CELLULAR GENES INVOLVED IN THYMIC RECONSTITUTION
  AND IMMUNE MODULATION
• Murine models of transient thymic atrophy
• low-dose irradiation dexamethasone estrogen.
• Use models to identify salvage mechanisms
  important for thymic regeneration.

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Marina Zaitseva (Senior Satff Fellow)

• CELLULAR GENES INVOLVED IN IMMUNE
  RECONSTITUTION
• ongoing experiments in irradiated mice
  reconstitution of T cells in the Gut-associated
  lymphoid tissues

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SECTION OF RETROVIRAL PATHOGENESIS Keith Peden
(PI)

• Safety of tumorigenic cell substrates for
  vaccine manufacture
• SV40 contamination in human vaccines
• HIV coreceptor evolution and pathogenesis

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Keith Peden Accomplishments

• Animal models to assess the oncogenic
  activity of cellular DNA
• - combination of oncogene-expressing plasmids
  induced tumors in newborn mice.
• ready to test DNA from new cell-substrate
• Quantitative assays to measure infectivity of
  integrated retroviral DNA
• - estimates for safe levels of residual
  cell-substrate DNA in viral vaccines
• - tools to evaluate removal of cellular DNA

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Keith Peden Accomplishments (2)

• quantitative assays to detect the presence of
  primate polyomavirus DNA in biological specimens
• single-cycle, reporter-gene based neutralization
  assays for BKV, JCV, and SV40

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MOLECULAR RETROVIROLOGY SECTION Arifa Khan
(PI) Accomplishments

• Simian Foamy Virus Transmission Studies
• - assess risk of human infection by
  SFV-infected blood donors.
• Studies of Simian Foamy Virus Replication
• - potential risk of SFV propagation in simian
  and human cells used for vaccine manufacturing.

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Arifa Khan Accomplishments

• Strategies for Detection of Infectious Agents
  in Vaccine Cell Substrates
• quantitative assays for detection of
  retroviruses
• induction of endogenous retroviruses in cells
  from different animal species
• induction of HHV-8 as a model of latent DNA virus