Abstract for the RCE

Bacillus anthracis Host Interactions

Discovery of Subunit Vaccine Candidates                             against Glanders

Alphavirus Vaccines for Biodefense

Novel Genetic Tools for Viral Biodefense

Development and Evaluation of Human
                     Brucellosis Vaccines

Rapid Diagnostic Tools for Q Fever

New Diagnostic Methods for Accute Rickettsial
                      Infections

Risks and Interventions for Pandemic Influenza

Development of Novel Pseudoinfectious Flavivirus                             Vaccines

Development of Diagnostic Reagents for the detection
                            of Francisella and
                             Francisella Infection

Toward Control of Rift Valley Fever Virus
                             Replication

Novel Vaccine Technology for Biodefense

Nucleocapsid-specific Small Molecule Inhibitors
                             of the Bunyaviridae

New Technologies for Creating Affinity Reagents

New Opportunities Projects

Identification and Characterization of Novel
                             Flavivirus Antivirals

Biosafety Containment Training Program

Passive Immunotherapeutics for
                             Select Agents

Preclinical Testing of YF17D/LAS, a Bivalent
                              Vaccine for Lassa and
                             Yellow Fever

Risks and Interventions for Pandemic Influenza

Collaborating Institution: University of Texas Medical Branch at Galveston (UTMB), Galveston, TX

Principal Investigator: Norbert Roberts Jr., MD

Co-Investigators:

a) Erich Hoffmann, PhD – St. Jude Children’s Research Hospital, Memphis, TN
b) Joan Nichols, PhD – UTMB, Galveston, TX
c) Michael Holbrook, PhD – UTMB, Galveston, TX
d) Robert Webster, PhD – St. Jude Children’s Research Hospital, Memphis, TN

Expected Product: Therapeutics and vaccine candidates for the treatment and prevention of pandemic influenza.

Description: A future natural influenza pandemic is inevitable, and the risk appears to be very high at the current time because of the widespread avian influenza outbreak. Direct infections of humans has occurred in countries in Southeast Asia and the Middle East since 2004, with >58% mortality for the documented human cases. The H5N1 avian virus has spread throughout Asia in poultry populations. There is increasing concern that the widespread outbreak of avian H5N1 in Asia will lead to co-infection of humans concurrently infected with human H1N1 and H3N2 strains, resulting in reassortant virus strains that can accomplish human-to-human spread and initiate the next influenza pandemic, with increased mortality (even if not fully 58%) for those infected.
Information regarding the potential avian–human reassortant combinations is key to establishing pandemic preparedness, including assessment of susceptibility of the likely strains to licensed or developmental antiviral agents, and identification of the most important reassortant strains for targeted vaccine development.
The hypothesis to be tested is whether human (H1N1 or H3N2) and avian H5N1 influenza virus genes are compatible and have the potential to generate a pandemic influenza virus. The available information would suggest that this should be very likely but we do not know if it is possible since not all influenza gene combinations are necessarily compatible. The specific aims of this project are to: (1) determine the potential for reassortment to occur between current human (H1N1 or H3N2) influenza viruses and an avian H5N1 influenza virus from a human case of infection in Vietnam and/or Indonesia; (2) determine if the resultant reassortant viruses are pathogenic in embryonated chicken eggs and mammalian cells, including human leukocytes; (3) determine if the resultant reassortant viruses are infectious for mice without adaptation and to determine whether they are highly pathogenic for the mice; and (4) determine if the resultant reassortant viruses are susceptible to current antiviral agents, such as the licensed neuraminidase inhibitors, or agents in development.
The studies represent a collaborative effort of investigators from the University of Texas Medical Branch and St. Jude Children’s Research Hospital who have expertise most relevant to the studies. The studies would use high biocontainment facilities at both institutions (BSL4 and BSL3-enhanced, respectively) as well as analyses of cells and viruses, rendered (and assured to be) non-infectious, in BSL2 laboratories at both institutions.