The NIH role in biodefense research is similar to its role in biomedical research in general; namely, to support basic scientific discovery, applied research and early-stage development activities that start new vaccines and drugs down the pathway toward approval.  Early-stage development activities that the NIH often supports include preclinical testing, animal model development, and establishment of pilot lot-scale manufacturing processes.  Late-stage advanced product development, such as commercial-scale process development and validation, is usually left to industry.  On rare occasions, however, the NIH has supported late-stage medical countermeasure development activities.  For example, in 2003, the NIH awarded milestone-driven contracts to two companies, Avecia and VaxGen, Inc., for late-stage advanced development of second-generation anthrax vaccines.  These contracts predated the Project BioShield Act of 2004.

The vaccines are based on a purified, recombinant (r) anthrax protein called Protective Antigen (PA), against which the body generates a strong antibody response; studies conducted in the 1990s showed that rPA vaccines could protect animals exposed experimentally to airborne anthrax spores from developing anthrax disease.  The Avecia and VaxGen contracts supported activities such as advanced manufacturing process development, Phase II clinical trials, and advanced assay development.  As noted above, NIH funding of late-stage advanced development for biodefense countermeasures is the exception rather than the rule.

RESEARCH PROGRESS

NIH research has yielded substantial scientific advances in the effort to counter emerging public health threats.  For example, new or improved candidate vaccines and therapies against smallpox and Ebola virus have shown great promise.  Among these is ST-246, a promising smallpox drug candidate that has protected nonhuman primates from what would otherwise be a lethal exposure to live smallpox virus, and that is now in human clinical trials.  Basic research also has proceeded rapidly.  NIH-supported researchers recently determined the structure of botulinum toxin—a Category A bioterror threat agent and the cause of botulism—as it binds to its receptor protein on nerve cells; these findings may lead to the development of new drugs to treat botulism.  Further, an NIH program that screens both approved drugs and new drug candidates has identified several promising anti-influenza drug candidates, including FluDase (which binds host cell receptors to prevent viral entry), T-705 (which inhibits replication of viral RNA) and Peramavir (which inhibits an influenza enzyme called neuraminidase).  All three of these influenza drug candidates are undergoing further development in partnership with industry sponsors.

With regard to the development of medical countermeasures against radiological, nuclear, and chemical threats, the NIH has established eight Centers for Medical Countermeasures against Radiation, and four Centers for Countermeasures against Chemical Threats.  Basic and applied research conducted in these centers and elsewhere is moving forward rapidly.  For example, researchers supported by one of these Centers recently characterized changes in gene activity in mice exposed to different doses of ionizing radiation and in cancer patients undergoing radiation therapy; these results may lead eventually to a diagnostic test to distinguish people who have suffered serious radiation exposure from those who have not prior to the onset of clinical illness.  That capability would allow treatments to be efficiently directed early on to those who need them most following a radiological incident.

NIH ROLE IN BIOSHIELD AND BARDA

Two landmark pieces of legislation designed to speed the development, approval, and acquisition of biodefense and emerging infections countermeasures have been enacted in recent years: the Project BioShield Act (Public Law 108-276), which became law in July 2004, and the Pandemic and All-Hazards Preparedness Act (Public Law 109-417), which became law in December 2006.

The BioShield legislation provided HHS and its constituent agencies with several new authorities regarding medical countermeasures against a terrorist attack with a biological, chemical, nuclear, or radiological agent or device.  Three of these authorities were of particular relevance to the NIH.  First, BioShield provided the NIH additional flexibility in awarding contracts, cooperative agreements, and grants for research and development of critical medical countermeasures.   Second, BioShield gave the NIH streamlined personnel authority that has allowed expedited hiring to fill key biodefense positions.  Third, BioShield provided the NIH with additional authority for the construction of research facilities.  The NIH has used all three of these authorities in carrying out its biodefense and emerging infections research and development responsibilities.  

Perhaps the most important provision of BioShield was the establishment of a secure funding source at HHS for the purchase of critical medical countermeasures.  Many pharmaceutical and biotechnology companies have been willing to help in the development of biodefense countermeasures, but they needed reasonable assurances that a market for these products would, in fact, exist should they invest the resources necessary to fully develop them.  To provide these incentives, BioShield established a Special Reserve Fund for the purchase of biodefense countermeasures to be placed in the Strategic National Stockpile for use in an emergency.

Procurement contracts under BioShield are developed and awarded by the HHS Office of the Assistant Secretary for Preparedness and Response (ASPR).  As is the case with other scientists within the Federal government and particularly within HHS, NIH personnel often serve as subject matter experts, consultants, and members of committees and boards that participate in the planning and execution of the HHS preparedness activities, including the development of contracts for BioShield acquisitions.  Ultimately, however, the decisions regarding acquisitions are made by the Office of the ASPR.

Title IV of the Pandemic and All-Hazards Preparedness Act established BARDA within HHS.  When BARDA is fully implemented, the Office of the ASPR will administer the Biodefense Medical Countermeasure Development Fund to support late-stage advanced product development.  Because the NIH is likely to have played a role in earlier phases of development of some of the products that BARDA might support, the NIH will coordinate with BARDA staff.  However, all decisions concerning products to be supported by BARDA will be made in the Office of the ASPR.

CONCLUSION

Emerging and re-emerging public health threats pose a perpetual challenge.  At one time, some in public health thought it might be possible eventually to “close the book” on the study of infectious diseases because of advances in therapies and vaccines.  However, it is now clear that naturally emerging and re-emerging infections will challenge us for the foreseeable future, as will threats from deliberately disseminated infectious diseases, chemical, or radiological terrorist attacks.  The task for the NIH is to continue building a strong foundation of basic and applied research and development that is needed to counter these threats, and also to be nimble enough to respond with speed and precision to new threats as they arise.  NIH efforts to address these challenges complement those of our colleagues in ASPR, CDC, FDA and other agencies in the Federal government to protect the health and safety of our Nation.

Last revised: August 29,2008