Overview of the Division of Viral Products
Jerry P. Weir, Ph.D.Director
Division of Viral Products/OVRR/CBER/FDA
The Division of Viral Products
Overview of the Division’s Mission, Responsibilities, and Public Health Impact
Overview of the Division’s Research Programs, Priority Areas of Focus, and Examples of Recent Accomplishments and Impact
Mission
Regulate viral vaccines and related biological products, ensuring their safety and efficacy for human use
Facilitate the development, evaluation, and licensure of new viral vaccines that positively impact the public health
Division of Viral ProductsResponsibilities
Investigational New Drug (IND) and Biologics License Application (BLA) review, and other pre-marketing activities (e.g., pre-IND)
BLA supplement review, lot release review and testing, and other post-marketing activities (e.g., Biological product deviations)
Manufacturer inspections (pre- and post-licensure) Consultation with other public health agencies (e.g., WHO,
CDC, NIBSC) Conduct research related to the development,
manufacturing, evaluation, and testing of viral vaccines
Licensed Viral Vaccines
Hepatitis Viruses Hepatitis A Hepatitis B HepA/HepB HepB-Hib DTaP-HepB-IPV
Vector-Borne Viral Diseases Yellow Fever Japanese Encephalitis Virus
DNA Viruses Varicella Virus Smallpox
Childhood Viruses Inactivated poliovirus Measles, Mumps, rubella Rotavirus
Respiratory Viruses Inactivated Influenza Live attenuated influenza
Other Viral Vaccines Rabies
Viral Vaccines Under Development
Hepatitis Viruses Hepatitis C Hepatitis E
Vector-Borne Viral Diseases Dengue West Nile Virus
DNA Viruses Human Papillomavirus Herpes Simplex Cytomegalovirus New smallpox vaccines
Childhood Viruses New Rotavirus vaccines
HIV Respiratory Viruses
New Influenza vaccines Pandemic influenza vaccines Respiratory Syncytial Virus Parainfluenza virus
Vaccines for Emerging Diseases and agents of Bioterrorism Ebola and other
hemorrhagic fevers Venezuelan Equine
Encephalitis Virus and other encephalitis causing viruses
The Division of Viral Products
Overview of the Division’s Mission, Responsibilities, and Public Health Impact
Overview of the Division’s Research Programs, Priority Areas of Focus, and Examples of Recent Accomplishments and Impact
Division of Viral ProductsSnapshot
7 Laboratories 17 Tenured Principal Investigators 67 Full-time equivalent staff (April 2006) > 50 Contract staff (e.g., post-doctoral fellows) ~ 140 publications (last 2 years) > $3,000,000 grants and contracts (FY05)
Researcher/Reviewer Model Review workload (e.g., INDs, BLAs, post-marketing) Mission-relevant research Outreach and collaboration (e.g., expert consultants to
WHO)
The Role of Research in the Division of Viral Products
Research and laboratory activities complement the regulatory mission
Address issues related to regulated viral vaccines Anticipate and address issues related to the development
and evaluation of new viral vaccine products General issues applicable to many products or product classes
(e.g., cell substrate issues, improved test methods, etc.) Specific product issues (correlates of protection necessary for
efficacy evaluation, animal models necessary for animal rule implementation, etc.)
Research efforts prioritized to maximize impact Availability of expertise Appropriateness of effort Competing demands
Division of Viral ProductsResearch Activities
Vaccine safety (e.g., evaluation of cell substrates) Vaccine efficacy (e.g., identification of correlates of
protection, development of animal models predictive of efficacy)
Reagent preparation (e.g., influenza vaccines) Development and evaluation of new methods and assays
for product characterization Issues related to vaccine development for emerging
diseases (e.g., pandemic influenza, HIV, West Nile virus) and Bioterrorism agents
Novel vaccination strategies and technologies
Division of Viral Products Laboratories
Jerry P. Weir, Ph.D., Director
Phil Krause, M.D., Deputy Director
Laboratory of Hepatitis Viruses
Steve Feinstone, M.D., ChiefLaboratory of Vector-Borne Viral Diseases
Lewis Markoff, M.D., Chief
Laboratory of Retroviruses
Hana Golding, Ph.D, Chief
Laboratory of DNA Viruses
Andrew Lewis, M.D., Chief
Laboratory of Respiratory Viral Diseases
Zhiping Ye, M.D., Chief (Acting)
Laboratory of Immunoregulation
Ira Berkower, M.D., Chief
Laboratory of Methods Development
Konstantin Chumakov, Ph.D., Chief
Laboratory of Vector Borne Viral Diseases
Areas of Research Characterization of candidate
live, attenuated dengue and West Nile virus vaccines.
Mechanism by which flaviviruses repair attenuating 3'terminal deletions of genome RNA.
Virion morphogenesis. Effect of quasi-species
character on phenotype. Development of an ELISA-
based potency assay for rabies vaccines.
Laboratory of Vector Borne Viral Diseases (continued)
Recent Accomplishments Determined that processing of
dengue structural proteins, envelope (E), pre-M (M), and capsid (C), requires the cellular enzyme signal peptidase
Identified structures in the 3’ non-coding region of the Dengue genomic RNA required for viral RNA replication
Demonstrated that the virus encoded RdRp contains an activity to repair 3'terminal deletions of virus RNA
Demonstrated that specific mutations in the capsid protein abrogate attachment, entry, or uncoating in monkey cells but not mosquito cells
Laboratory of Hepatitis Viruses
Areas of Research Vaccine strategies to prevent
HCV infection Development of mouse models
for HCV infection to replace the chimpanzee
Development of in vitro culture systems to study antibody neutralization of HCV
Biomarkers for HCV protection and HBV/HCV related hepatocellular carcinoma
Rotavirus-cell interactions Rotavirus attenuation markers
Laboratory of HepatitisViruses (continued)
Recent Accomplishments Defined pathogenesis and immune responses to HCV in chimp
model Demonstrated that protective T-cell mediated immunity occurs in
chimpanzees that spontaneously clear HCV infection Established that neutralizing antibody to HCV does not play a role in
clearance of virus but can control viral replication in vaccinated chimpanzees
Established in vitro culture systems and transgenic mouse models for HCV study
Demonstrated that T-cell vaccines can modify HCV infections and that CD4+ T cell escape is a mechanism of T-cell vaccine failure
Demonstrated that the N- and C-terminal regions of rotavirus NSP5 are determinants of viroplasm formation and that VP4 translocates to cellular peroxisomes by PTS1
Laboratory of Immunoregulation
Areas of Research Structure-function
analysis of HIV envelope glycoproteins
Vaccination strategies to enhance vaccine immunogenicity
Dissecting the neutralizing antibody response to vaccinia virus
gp120 particles HBsAg particles
Laboratory ofImmunoregulation (continued)
Recent Accomplishments Developed a novel method
for forming virus-like particles
Expressed HIV gp120 and gp41 at a lipid-water interface
Identified forms of gp120 with increased antigenicity and immunogenicity
Identified a novel mechanism of resistance to HIV fusion inhibitors
Evaluated the role of antibodies to A27 in Dryvax-induced protection
Laboratory of Respiratory Viral Diseases
Areas of Research Prepare and distribute influenza virus
reagents to determine purity and strength of influenza vaccines
Perform serology studies in support of influenza strain selection
Develop new high growth influenza virus strains for vaccines and determine properties for optimal growth in eggs and tissue culture
Evaluate new vaccine strategies Identify cellular receptors for
respiratory syncytial virus (RSV) and determine antigenic structure of RSV glycoproteins
Develop serological methods for vaccine trial evaluation
Laboratory of Respiratory Viral Diseases (continued)
Recent Accomplishments Prepared potency reagents (e.g., strain-
specific antisera) for seasonal influenza vaccine and possible pandemic strains
Developed attenuated donor influenza virus that can be used for preparation of pandemic vaccines
Demonstrated improved efficacy of influenza DNA vaccines by co-expression of multiple genes
Identified amino acid motifs that contribute to high growth of influenza B in eggs
Demonstrated that HSPGs bind RSV glycoproteins and identified binding domains that block attachment
Laboratory of MethodDevelopment
Areas of Research Microarrays and other molecular methods for analysis of
pathogens Genotyping of viruses and bacteria Identification of Mycoplasmas Genetic stability of live viral vaccines
Immunological test methods development New animal model development Neurotoxicity assay development
Laboratory of MethodDevelopment (continued)
Recent Accomplishments Identified mutation hot-spots in vaccine-
derived poliovirus (OPV) Assessed the mucosal immune response to
IPV by direct PCR analysis of stool samples of vaccinees
Used Block-ELISA profiling of IPV to monitor consistency of IPV production and to study antigenic properties
Evaluated immunogenicity of new Sabin IPV (with and without adjuvants) in Tg-mouse potency test
Developed rapid microarray-based genotyping of influenza virus strains
Developed new neurotoxicity test for mumps virus
Developed mumps virus neutralization assay for assessing protective immune responses
Laboratory of Retrovirus Research
Areas of Research Development of assays for HIV and
smallpox clinical trial evaluation Identification and characterization of
adjuvants Activity and safety of DNA vaccines
and CpG oligodeoxynucleotides Safety and evaluation of cell substrates
used for vaccine production Retrovirus transmission
Laboratory of RetrovirusResearch (continued)
Recent Accomplishments Developed a method to distinguish HIV infection
from vaccine response in clinical trials Developed a method for rapid measurement of
neutralizing antibody following smallpox vaccination Demonstrated that administration of CpG
oligodeoxynucleotides preferentially activates IFNγ secreting cells, increases antigen-specific antibody responses, and improves the protective efficacy of pathogen-specific vaccines
Developed assays to assess DNA oncogenicity Established induction conditions for detecting occult
retroviruses in cell substrates
Laboratory of DNA Viruses
Areas of Research Evaluation of cell substrates
used for vaccine manufacture Developing methods to evaluate
the risks posed by the use of neoplastic cells for production of viral vaccines
Detection of adventitious agents
Mechanisms of viral latency Immunogenicity and pre-
clinical efficacy of new-generation smallpox vaccines
Evaluation of novel herpesvirus vaccination strategies
Laboratory of DNAViruses (continued)
Recent Accomplishments Developed methods to evaluate neoplastic cells
used in viral vaccine production (e.g., tumorigenicity and oncogenicity assays)
Developed standardized Q-PCR assays for detection of specific polyomaviruses
Developed novel methods for the detection of non-specific adventitious agents
Identified the major antigens of the humoral immune response to smallpox vaccination
Demonstrated that new-generation smallpox vaccines (e.g., MVA) elicit levels of protective immunity comparable to traditional smallpox vaccines in animal models of efficacy
Demonstrated that novel vaccination strategies (e.g., prime-boost immunization) result in enhanced immune responses
Summary The research programs and laboratory activities in
the Division of Viral Products support the regulatory mission of the Office of Vaccines and CBER Ensures the safety and efficacy of regulated viral vaccine
products, and
Facilitates the development and evaluation of new virus vaccine products