Brian R. Murphy, M.D., Co-Chief
Robert H. Purcell, M.D., Co-Chief
Established in 1942, the Laboratory of Infectious Diseases (LID) has a long history of vaccine development and identification of new agents of viral diseases. The LID is noted for undertaking high-risk, high-reward programs that require extraordinary time and resource commitments, such as programs to develop vaccines for viral hepatitis, severe childhood respiratory diseases, and viral gastroenteritis.
The LID also has a long-term commitment to investigating host immune response to viruses; the pathogenesis of viral infections; and the molecular biology, antigenic diversity, and genetics of viruses. This work is augmented by an extensive clinical program, permitting investigations of pathogenesis and immunity to viral infection in the human host and testing of candidate vaccines in target populations.
While moving forward with important long-term commitments, LID scientists also are responding to new challenges presented by the emergence of new viral agents and NIAID’s biodefense mandate. For example, the LID has initiated programs to develop vaccines for pandemic influenza and SARS-CoV. West Nile virus (WNV) was added to ongoing flavivirus vaccine development efforts and human metapneumovirus (HMPV) was added to the paramyxovirus vaccine program.
In addition, a program originally designed to develop immunotherapies and immunoprophylaxis for hepatitis was expanded after September 11, 2001, to include therapies for emerging and select agents. It now includes over 20 agents, such as anthrax and botulinum toxins, WNV, and tick-borne and St. Louis encephalitis viruses.
Another new LID program is developing paramyxovirus vectors able to infect all humans regardless of their previous experience with human paramyxoviruses. Such vectors can be made into vaccines for diseases caused by SARS-CoV, Ebola virus, Marburg virus, and other viruses by adding genes for the major protective antigen(s) from these highly pathogenic viruses to the vector.
The LID has made significant progress in understanding the biology, pathogenesis, and immune response to many groups of both positive- and negative-strand RNA viruses. These discoveries contribute to our conceptual and technological context of vaccine development, as well as to policy development for global virus control and eradication programs. Examples of LID accomplishments follow:
- Both a licensed hepatitis A vaccine (HAVrix®) and monoclonal antibody to RSV (Synagis®) continue to be widely used.
- A live attenuated trivalent influenza vaccine, FluMist®, was licensed by MedImmune, Inc. LID developed this vaccine from 1975 to 1995 with participation of the extramural component of NIAID. This is a prime example of a many-decade LID commitment to the development of a specific vaccine.
- Bovine- and rhesus-based rotavirus vaccines are being widely licensed internationally as it has become clear that these vaccines can be safely administered using a modified immunization schedule.
- A recombinant, live attenuated RSV vaccine was shown to be safe and immunogenic in 1- to 2-month-old infants.
- A hepatitis E vaccine, licensed to GlaxoSmithKline, proved highly effective in preventing hepatitis E in a field trial in Nepal.
- The major immunologic mediator of protection against SARS-CoV was identified. Four different immunization strategies and a protective human monoclonal antibody were developed.
- Vaccine candidates for WNV have been generated, and one is licensed and in clinical trial.
- HMPV was completely sequenced and recovered from cDNA. The extent of antigenic diversity between the two HMPV lineages was defined, the major protective antigen was identified, and three promising vaccine candidates were generated.
- A tetravalent live attenuated dengue virus vaccine has been formulated that is attenuated and immunogenic in rhesus monkeys. This tetravalent dengue virus vaccine is being licensed throughout the world.
- A live attenuated PIV3 vaccine has passed phase II trials in infants. Recombinant live attenuated, genetically stable PIV1 and PIV2 vaccine candidates have been generated. Live attenuated recombinant PIV3 vaccine candidates have been recovered directly in qualified Vero cells, permitting evaluation in phase III trials.
Although the major emphasis of LID is the development of vaccines and other immunoprophylactic agents, we recognize the importance of maintaining a broad and diverse scientific environment that supports and stimulates the activities of the vaccine programs. Other ongoing studies include microarray analysis of liver biopsies to study host response to viral hepatitis; investigations of virus-insect vector interactions for WNV, St. Louis encephalitis virus, and the dengue viruses; and, as part of our virus discovery program, efforts to transmit Kawasaki disease to nonhuman primates.
Office of the Co-Chiefs
Brian R. Murphy, M.D.
Robert H. Purcell, M.D.
Epidemiology Section
Albert Z. Kapikian, M.D.
John T. Patton, Ph.D.
Kim Y. Green, Ph.D.
Yasutaka Hoshino, D.V.M.
Hepatitis Viruses Section/Molecular Hepatitis Section
Robert H. Purcell, M.D.
Suzanne U. Emerson, Ph.D.
Jens Bukh, M.D.
Molecular Viral Biology Section
Ching-Juh Lai, Ph.D.
Picornavirus Replication Section
Ellie Ehrenfeld, Ph.D.
Respiratory Viruses Section
Brian R. Murphy, M.D.
Peter L. Collins, Ph.D.
Alexander G. Pletnev, Ph.D.
Kanta Subbarao, M.D., M.P.H.
Jeffery K. Taubenberger, M.D., Ph.D.
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