Biodefense and Emerging Infectious Diseases

NIAID, part of the National Institutes of Health (NIH), conducts and supports basic research to better understand viruses, bacteria, and other infectious agents that cause diseases of public health concern. This research provides the foundation for developing medical products and strategies to diagnose, treat, and prevent a wide range of infectious diseases, whether those diseases emerge naturally or are deliberately introduced into a population through an act of bioterrorism. No matter what the source of the infectious threat, the research approach is the same: understand the infectious agent and how it causes disease, and develop tools to diagnose, treat, and prevent illness caused by that microbe.

The NIAID role in supporting basic research leading to the development of medical products and strategies to counter bioterrorism and emerging and re-emerging infectious diseases is part of a larger national strategy involving many U.S. government agencies. The U.S. Department of Homeland Security (DHS) is responsible for determining which biological agents pose the greatest threat to U.S. national security. The U.S. Department of Health and Human Services (HHS) then assesses the potential public health impact of each of the high-priority threats and establishes requirements for developing the most relevant medical countermeasures (for example, treatments and vaccines) for each agent.

Overall responsibility for coordinating research, development, acquisition, storage, maintenance, deployment, and guidance for using biodefense-related medical products also rests with HHS, specifically the Office of the Assistant Secretary for Preparedness and Response (ASPR). Within ASPR, the Biomedical Advanced Research and Development Authority (BARDA) provides an integrated, systematic approach to developing and purchasing the vaccines, drugs, therapies, and diagnostic tools needed for public health medical emergencies. BARDA manages Project BioShield, which includes the advanced development and procurement of medical countermeasures for chemical, biological, radiological, and nuclear agents. In addition, BARDA manages the advanced development and procurement of medical countermeasures for pandemic influenza and other emerging infectious diseases that fall outside the auspices of Project BioShield.

New medical countermeasures, which are subject to regulatory approval by the Food and Drug Administration (FDA), may then be purchased by the government for the Strategic National Stockpile (SNS). The SNS—the repository of medical countermeasures that can be quickly deployed by the government during a public health emergency—is managed by the Centers for Disease Control and Prevention (CDC), which has primary federal responsibility for preparing for and responding to public health emergencies. CDC also regulates the possession, use, and transfer of biological agents and toxins that could pose a severe threat to public health and safety. Certain of these materials might or could be under investigation by NIAID-supported researchers working in high-containment laboratories.

The NIAID role in supporting biodefense and emerging infectious disease research has not changed over the past 10 years; however, the focus of the research has evolved during that time.

Following the 9/11 terrorist attacks in 2001 and the anthrax mailings soon thereafter, the Administration, with bipartisan support from Congress, provided $1.5 billion in newly appropriated money to NIAID in fiscal year 2003 to conduct and fund research related to biodefense and emerging infectious diseases. NIAID was chosen to receive this money because of the Institute’s longstanding and successful track record regarding research on infectious diseases in general and on emerging and re-emerging infectious agents in particular. (The Institute was established as part of NIH in 1948.)

An important element in the decision to give NIAID these funds was broad agreement that research on naturally occurring emerging and re-emerging infectious diseases should be included in this new mandate. In this sense, NIAID received a “dual mandate” to conduct research on important infectious agents that might be deliberately introduced into a community through a bioterrorist event or that might emerge or re-emerge naturally.

In 2001, the prevailing U.S. model for developing medical countermeasures for a potential bioterrorist attack was that of the U.S. Department of Defense. In this model, vaccines were developed, stockpiled, and given prophylatically to our armed forces to protect them from known or suspected agents of bioterrorism. HHS, of which NIH is a part, initially adopted this model and directed NIAID to fund efforts toward developing vaccines against those infectious agents that were identified, through intelligence channels, to be of most concern regarding the public. As a result, NIAID research efforts during the early years of biodefense were focused on developing a set of vaccines for specific pathogens. At that time, the intent was to prepare to be able to protect the public if necessary by pre-emptively vaccinating the U.S. population against the infectious agents with bioterrorism potential of greatest concern.

However, over time the collective thinking—which included input from the nation’s top scientists—evolved, and the view emerged that developing the ability to pre-emptively vaccinate the public against the threats of greatest concern (known as Category A agents) was not a pragmatic, sustainable, or comprehensive approach. Thus, NIAID shifted its research approach on biodefense and emerging infectious diseases to align with its long-established research mission. Instead of focusing on agent-specific vaccines, the Institute turned its focus to support the fundamental research needed to better understand infectious agents. The goal of this basic research is to lay the foundation for developing broad-spectrum antibiotics and antivirals—drugs that can prevent or treat diseases caused by multiple types of bacteria or viruses, respectively. In addition, NIAID intensified its efforts to develop multi-platform technologies that can be widely applied, for example, to more efficiently develop diagnostics and vaccines against a wide variety of infectious agents.

For more information view Category A agents.

Infectious diseases research in general has benefited considerably from the influx of the additional NIAID biodefense and emerging infectious diseases funding. The most important achievement has been an increase in our knowledge of infectious agents of all kinds and in our ability to respond to them. Basic research on the biology of specific pathogens and on the human immune system, and on the complex relationship between the two, have opened up new ways of thinking about infectious diseases and, with that, new ways to control them. This knowledge was generated through investments in multidisciplinary research consortia to study high-priority infectious agents and in the biocontainment facilities in which to study them, and in the development of research reagents and resources for use by the scientific community conducting this research. These investments have also fueled our innovative product development approach, including the movement from the “one bug-one drug” approach toward a more flexible and broad strategy. This approach involves developing medical countermeasures by integrating genomic and proteomic technologies; using sophisticated genome sequencing technologies to identify new and common drug and vaccine targets; and creating vaccine platforms and other technologies that can be widely applied to develop medical products and reduce production time and costs. This broad-spectrum strategy recognizes both the expanding range of biological threats and the limited resources available to address each individual disease-causing pathogen. Advances in infrastructure and resources available to the research community can be seen at Research Infrastructure and a selection of specific research accomplishments can be seen at Key NIAID Biodefense Accomplishments Since 2001.

Overall, the United States is much better prepared to respond to an infectious disease threat today than it was 10 years ago in part because of the strong investment in basic and applied research, product development, and technology development for biodefense and emerging infectious diseases. In addition, the United States now has a much more integrated and coordinated approach to addressing public health crises as witnessed during the SARS epidemic, the pandemic flu preparedness efforts triggered by the appearance of H5N1 influenza, and the 2009 pandemic H1N1 influenza pandemic.

Developing medical countermeasures, such as diagnostics, treatments, and vaccines, that can protect the public from potential infectious threats is an integrated process. Basic research, the focus of NIAID-supported research efforts, lays the groundwork by generating a greater understanding of infectious diseases as well as new concepts about the diagnosis, treatment and prevention of them, based on studies of the disease-causing pathogen and the human immune response to it. Applied research builds on basic research by validating innovative diagnostic, treatment, and prevention concepts in model systems, and testing them in practical research settings. Successful candidates move into advanced product development, where they are manufactured and evaluated for safety and efficacy in animals and humans according to strict guidelines and regulations.

NIAID works with partners in the private and public sectors and collaborates with other agencies and organizations to ensure that the fruits of the most promising NIAID-supported basic research can be rapidly translated into products. NIAID efforts have been closely aligned with the HHS Public Health Emergency Medical Countermeasures Enterprise (PHEMCE) Strategy for Chemical, Biological, Radiological and Nuclear Threats, the HHS PHEMCE Implementation Plan, and the Homeland Security Presidential Directive (HSPD)-18, which outline strategies for identifying what medical countermeasures are required and establishing priorities for their research, development, and acquisition.

NIAID also funds the efforts of dozens of biotechnology and other pharmaceutical entities to develop those concepts into practical medical products. In addition, NIAID maintains specialized support services to assist researchers and product developers throughout the product development lifecycle. Ultimately, NIAID transfers the most promising medical product concepts to other entities, both public and private, to complete commercial development activities necessary for approval by regulatory agencies such as FDA.

NIAID has established a comprehensive research infrastructure with extensive resources that support all levels of research and pursuit of multiple broad-spectrum concepts. Examples of this infrastructure include the following:

• Regional Centers of Excellence (RCEs) for Biodefense and Emerging Infectious Diseases—Eleven multidisciplinary research teams, based at universities nationwide, provide resources and communication systems that can be rapidly mobilized and coordinated with regional and local systems in response to an urgent public health event. These centers alone have been responsible for a vast array of research advances captured in more than 2,000 scientific publications to date.
• Cooperative Centers for Translational Research on Human Immunology and Biodefense—These eight centers further knowledge of human immune responses against infectious pathogens and the biological mechanisms behind those responses. The ultimate goal of these centers is to translate research on immunity to infection into clinical applications to protect the public against bioterrorist and naturally occurring infectious diseases threats.
• Biocontainment Research Laboratories
  • National Biocontainment Laboratories (NBLs) and Regional Biocontainment Laboratories (RBLs)—Two NIAID-funded biosafety level 4 (BSL-4) NBLs and 12 BSL-3 RBLs are available or under construction for research requiring high levels of containment. These laboratories are prepared to assist national, state and local public health efforts in the event of a bioterrorism or infectious disease emergency.
  • NIAID also has constructed or is in the process of constructing two BSL-4 and one BSL-3 biocontainment research facilities located in Maryland and Montana. These facilities are staffed by world-class NIAID scientists conducting research on biodefense and emerging and re-emerging infectious diseases.
• Vaccine and Treatment Evaluation Units—These clinical sites, located at universities nationwide, allow for extensive clinical trials capacity and expertise. They played a key role in testing the vaccine for the 2009 H1N1 influenza pandemic.
• The Biodefense and Emerging Infections Research Resources Repository offers reagents and information essential for studying emerging infectious diseases and biological threats.
• Preclinical resource services yield information that can be used to support Investigational New Drug applications for both candidate drugs and vaccines.
• Genomics and proteomics centers include the Microbial Sequencing Centers, the Pathogen Functional Genomics Resource Center, the Bioinformatics Resource Centers, and the Biodefense Proteomics Research Centers.
• The In Vitro and Animal Models for Emerging Infectious Diseases and Biodefense resource provides screening of potential therapeutics and the development of in vivo animal efficacy models for evaluating drugs and vaccines.
• The Immune Epitope Database is a public database that provides information on all published antibody and T-cell epitopes for Category A, B, and C pathogens and their toxins, and it also provides state-of-the-art epitope analysis tools.
• The NIH Tetramer Facility provides custom-made major histocompatibility complex (MHC) class I and class II tetramers for detecting and characterizing host T-cell responses to infectious agents.
• The NIAID Centers of Excellence for Influenza Research and Surveillance—These five centers, located at universities in the United States, conduct prospective international or domestic animal influenza surveillance to rapidly detect and characterize influenza viruses with pandemic potential. The centers also conduct research to enhance understanding of the molecular, ecological, or environmental factors that influence the pathogenesis, transmission, and evolution of influenza viruses; and that characterize the protective immune response.
• NIAID supports multiple training opportunities, ranging from basic introductory courses and workshops to two-year fellowships to provide professional training in biosafety and biocontainment.

The U.S. investment in biodefense and emerging infectious diseases research and product development has significantly benefited other areas of medicine. Many organisms under study and a host of other emerging infectious diseases and drug-resistant microbes are significant public health threats, both within the United States and in other parts of the world. Research on microbial biology and pathogenesis has enhanced the understanding of naturally occurring infectious diseases. Advances in developing diagnostics, vaccines, and therapeutics with broad-spectrum activity have had direct relevance to naturally occurring diseases, such as pandemic influenza and dengue, as well as spin-off benefits for developing other broad-spectrum products.

Broad-spectrum technologies that improve product stability, potency, and ease of use can be applied to many classes of new diagnostics, vaccines, and therapeutics, regardless of the disease target. The most obvious gain is for interventions to prevent, diagnose, and treat major microbial killers such as malaria, tuberculosis, and HIV/AIDS, as well as other emerging and re-emerging infectious diseases. Broad-spectrum platforms of these types are especially important in countries where public health infrastructure cannot support the delivery of products that require constant refrigeration or freezing, multiple doses, or advanced diagnostic equipment. Such platforms can reduce the time and cost of developing new products for many medical conditions.

In addition, basic research on host defenses is enhancing our understanding of the molecular and cellular mechanisms of the first-line, nonspecific innate immune system and its relationship to the specific or adaptive immune system, which can lead to improvements in the treatment and prevention of immune-mediated diseases, such as systemic lupus erythematosus, rheumatoid arthritis, and other autoimmune diseases. Finally, an improved understanding of how the human immune system is regulated may have applications for diseases such as cancer, immune-mediated neurological diseases, and allergic and hypersensitivity diseases, as well as for preventing rejection of transplanted organs.

Our biodefense and emerging infectious diseases research accomplishments have broad applications for infectious diseases as well as other areas of medical research. For example, NIAID-supported biodefense and emerging infectious disease research has yielded important insights into physiologic and pathogenic features common to many types of bacteria. The inherent links between emerging and re-emerging infectious diseases, whether naturally occurring or deliberately introduced into a community, demonstrate that learning about underlying principles and approaches is as important as determining microbe-specific information.

Selected examples of crossover research advances include the following:

• LJ001 (identified from a screen for inhibitors of Nipah virus), an investigational broad-spectrum antiviral drug that has potential against all known enveloped viruses, including Ebola, influenza, and HIV. ( For more information read "Researchers identify potential broad spectrum antiviral drug" from BMJ).
• Modified vaccinia Ankara (MVA) vaccine, a smallpox vaccine for immunocompromised individuals (in whom the traditional smallpox vaccine is contraindicated), in development as a platform for other infectious agents (HIV and respiratory syncytial virus) as well as for both prostate and breast cancer vaccines.
• An investigational antibiotic designed to boost the immune system to create an overpowering response against a variety of pathogenic bacteria as opposed to attacking a specific bacterium after infection.
• Salmonella typhimurium bacteria have shown promise as an oral delivery platform in a live, recombinant vaccine that both protects and has immuno-therapeutic effects against melanoma tumors in mice.
• Early research into development of anti-infective agents for specific biodefense-related Gram-negative bacteria may yield broadly applicable knowledge and products targeting common pathways for other types of Gram-negative bacteria that are not biodefense-related.
• Research into discovering and/or developing antiviral drugs for smallpox that inhibit host cell signal transduction may have implications for a new class of antiviral drugs effective against a range of viruses, and potentially may affect research on infectious agents other than viruses.

NIAID’s pathogen priority list is periodically reviewed and is subject to revision in conjunction with our federal partners, including DHS, which determines threat assessments, and CDC, which prepares for and responds to emerging pathogen threats in the United States.

When NIAID first published its Strategic Plan for Biodefense Research in 2002, it was largely focused on conducting basic research on specific high-priority pathogens and applying that research to the development of diagnostics, therapeutics, and vaccines targeting those pathogens. The 2007 update of this plan represented a shift from a “one bug-one drug” approach to a more flexible, broad-spectrum strategy that is applicable to all infectious diseases. This approach enables the research community to develop products effective against a variety of pathogens and toxins; find technologies that could be widely applied to improve multiple classes of products; and establish platforms that can reduce the time and cost of creating new products. This approach has applicability beyond specific biodefense-related needs. For example, it is relevant to developing new classes of antibiotics, finding effective new animal models to support drug and vaccine efficacy studies, and advancing the understanding of the innate and adaptive immune systems.

For more information, view the Pathogen Priority List.

The past decade of NIAID basic research investment in biodefense and emerging infectious diseases, combined with the revolutionary progress in fields such as genomics and proteomics, has created unprecedented scientific opportunities. We are in the midst of a 21st-century paradigm shift in research related to all infectious diseases. Looking ahead, NIAID will continue to move away from the “one bug-one drug” approach to infectious diseases and toward broad-based solutions, such as vaccine platforms and therapeutics that are effective against a range of disease agents.

NIAID also will continue to support research to advance scientific understanding of disease mechanisms and, in particular, the interface of microbiology and host immunity that results in disease. Given the limited repertoire of host defenses and immunological responses, the points of intersection between a microbe and its host suggest potential targets for developing novel approaches to broad-spectrum intervention. In addition to offering new modalities against existing public health and biodefense threats, these broad-based strategies will help us to develop medical countermeasures for unknown infectious agents that will emerge in the future, as well as help us to reduce the potential for drug resistance.