Influenza Research in NIAID Labs
DIR researchers are studying the basic biology of influenza, including its pathogenesis, immunogenicity, transmissibility and genetic variability; investigating host immune responses to the virus in animal models and in humans; developing vaccines to prevent influenza, especially strains with pandemic potential; and studying influenza epidemiology.
In DIR’s Laboratory of Infectious Diseases, two senior investigators lead our influenza-related research:
Dr. Kanta Subbarao leads a group working with MedImmune under a Cooperative Research and Development Agreement (CRADA) to generate candidate, live-attenuated vaccines for a broad range of influenza subtypes with pandemic potential. Five of these vaccine candidates have advanced to Phase I clinical trials.
Dr. Jeffery Taubenberger, formerly of the Armed Forces Institute of Pathology in Rockville, MD, joined the LID in 2006. His lab is studying the pathogenesis of influenza in diverse host species; influenza virus evolution and adaptation, especially the factors that lead to the emergence of pandemic strains; and the molecular basis for virulence of highly pathogenic influenza viruses, including the 1918 pandemic strain and H5N1 viruses.
In DIR’s Laboratory of Viral Diseases, Drs. Jack Bennink and Jonathan Yewdell lead investigations of the immunobiology of influenza A virus in mouse model systems. Specific topics include antigen processing and presentation of viral proteins to T cells, antigenic drift in influenza glycoproteins, the function of the PB1-F2 gene product in influenza pathogenicity, and the regulation of antiviral immunity by the nervous system.
The Division of Clinical Research (DCR) conducts clinical studies within NIAID’s Division of Intramural Research (DIR) and collaborates with clinical trial networks worldwide to develop vaccines, therapeutics and diagnostics. Learn more about influenza clinical studies being conducted by DCR.
In response to the need to develop improved influenza vaccines protective against both seasonal influenza and avian influenza strains with the potential for pandemic outbreaks, the Vaccine Research Center (VRC) has initiated a program to develop novel vaccine approaches.
The first VRC investigational vaccine for clinical evaluation is an H5 DNA vaccine that builds on the existing VRC DNA plasmid platform technology. On December 15, 2006, the VRC received notice from the Food and Drug Administration (FDA) that the VRC’s Investigational New Drug (IND) application for the H5 Influenza DNA vaccine was safe to proceed for clinical study. The VRC Clinical Trials Core started its first injection within two weeks. This investigational vaccine is the first product produced entirely within the VRC Vaccine Production Program (VPP) and the first vaccine manufactured at the VRC/VPP to be taken into a Phase I clinical study.
VRC is also developing and testing gene-based and protein-based vaccines to protect against multiple H5 strains. Structure-based modification of hemagglutinin (HA) specificity can guide the development of preemptive vaccines and therapeutic monoclonal antibodies that can be evaluated before the emergence of human-adapted H5 strains. Preclinical immunogenicity studies are underway testing vaccines consisting of H5 DNA alone; H5 protein alone; or an H5 DNA prime and recombinant adenoviral vector (rAd5) boost regimen encoding various gene products alone or in combination, including HA, NP and M2. Several initial candidate vaccines have shown promise in animal studies. NP and M2 will advance into clinical studies if ferret studies look as promising as mouse models with these genes in DNA/rAd.
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