May 7, 2003
Mr. Chairman and Members of the Committee, thank you for the opportunity to discuss how the National Institutes of Health (NIH) is responding to the global outbreak of Severe Acute Respiratory Syndrome, or SARS. I am pleased to appear today with my colleagues from our sister agencies, within the Department of Health and Human Services. As of April 29, 2003, 5462 cases of SARS have been reported across the globe, with 54 probable cases identified in the United States; there have been no deaths from SARS thus far reported in the United States. The relatively low number of probable cases reported in the United States is likely the result of early diagnoses and effective public health measures put in place by the CDC and state and local health authorities to contain the imported SARS cases and prevent secondary transmissions.
While travel alerts and advisories and recommended infection control measures can help slow the progression of the SARS epidemic, these alone are not long-term solutions to this new and unpredictable disease. Instead, we must develop safe and effective treatments and vaccines that can protect the American people. The SARS epidemic is still evolving and it is unclear whether the incidence of the diseases will decline, plateau or accelerate. Therefore we must be prepared for any eventuality.
Like HIV/AIDS, Ebola and West Nile virus, SARS reminds us that emerging and reemerging infectious diseases are constant threats to national and international public health. Dr. Gerberding and her CDC team, together with the World Health Organization (WHO) and others, have done an outstanding job in identifying and tracking the SARS epidemic, illuminating the clinical features and etiology of the disease, and providing the world with information about the epidemic in real time.
Complementing the efforts of the CDC and WHO, the National Institute of Allergy and Infectious Diseases (NIAID), a component of NIH, has a significant role in the efforts against SARS, notably in diagnostics, therapeutics and vaccine development, drug screening, and clinical research. As has been the case with other emerging infectious diseases, we anticipate that the strong NIAID research base in disciplines such as microbiology, immunology and infectious diseases will facilitate the development of new interventions to help counter SARS.
The CDC and WHO have accumulated evidence, which we now believe is close to definitive, that SARS is caused by a novel coronavirus that may have crossed species from an animal to humans, although this latter point has certainly not been proven. This hypothesis is based on the detection and isolation of coronaviruses from unrelated SARS patients from different countries and on the finding that SARS patients mount an immunological response to coronavirus as they proceed from the acute illness to the recovery or convalescent stage. Furthermore, data from the Netherlands show that non-human primates infected with this coronavirus develop a SARS-like disease, suggesting that this virus is the cause of SARS. Although some questions remain, the strong evidence for a causative role for a coronavirus has prompted the ongoing development of diagnostic tools, therapies, and vaccines that target coronaviruses.
Coronaviruses are best known as one of the causes of the common cold, a benign condition that very rarely results in life-threatening disease. The coronavirus associated with SARS is a type of coronavirus, possibly of animal origin, that has not been previously identified.
NIAID Research on SARS
Since the earliest indications that we were dealing with a new disease, very likely caused by a newly recognized virus, the NIAID has marshaled its resources to rapidly initiate the development of diagnostics, therapeutics, and vaccines against SARS. NIAID has assembled a multi-disciplinary working group to develop a broad-based program that addresses the research needed to combat SARS. Key intramural laboratories have begun to pursue a range of research strategies to develop a SARS vaccine as well as therapeutics, including immune-based therapies, and our extramural programs are poised to help as well. We also have initiated and expanded collaborations with our colleagues in other federal agencies, academia, and private industry. In addition, NIAID recently released three "Sources Sought" announcements, a special mechanism to rapidly identify contractors who can develop treatment strategies, vaccines, and antibody preparations to address SARS.
Surveillance and Epidemiology
It is anticipated that a sensitive and specific diagnostic test for SARS may be available within six to 12 months. Within one to three years, it may be possible to develop a rapid, accessible easy-to-use test for SARS that could be widely deployed in diverse healthcare settings.
Fortuitously, vaccines against common veterinary coronaviruses are routinely used to prevent serious diseases in young animals, such as a vaccine given to pigs to prevent serious enteric coronavirus disease. Insight from veterinary coronavirus vaccines could prove useful as we develop vaccines to protect humans.
To accelerate SARS vaccine research and development efforts, NIAID has initiated contracts and other relationships with companies, institutions and other organizations with specialized technologies, cell lines and containment facilities relevant to SARS research for the purpose of supporting the development of reagents needed for vaccine development, and developing animal models such as mice and relevant species of monkeys. For example, the NIAID Vaccine Research Center recently expanded an existing agreement with GenVec, a biopharmaceutical company in Gaithersburg, Maryland, to begin the development of a candidate vaccine against SARS. NIAID is negotiating with other companies to develop additional candidate vaccines. Another important component of SARS vaccine research will be to identify ways to generate mucosal immunity against the SARS coronavirus.
Within the next six to 12 months, NIAID anticipates that it will be possible to demonstrate whether an inactivated vaccine against SARS is a workable concept, e.g., to show that we can protect a monkey against the SARS virus. If so, Phase I trials of such a candidate vaccine can be accelerated. If research and development proceed on schedule and if animal testing is successful, a first-generation inactivated SARS vaccine could become available within several years.
In addition to antiviral drugs, NIAID is supporting the development of passive immunotherapy (monoclonal and polyclonal antibodies) as a therapy for SARS. Within the next one to three years, it may be possible to have available therapeutic monoclonal antibodies for SARS.
At the NIH Clinical Center in Bethesda, MD, and through the NIAID Collaborative Antiviral Study Group, NIH is developing protocols to admit SARS patients for evaluation and treatment, should this become necessary. This will be an opportunity to evaluate the pathogenesis of the illness and the efficacy of antiviral and immune-based therapies in patients with SARS. We also plan to evaluate approaches to improve management of patients with severe forms of the disease, such as the passive transfer of antibodies from SARS patients who have recovered from the disease.
In addition to ensuring state-of-the-art treatment of potential patients, our clinical experts will be able to study the clinical characteristics of patients with SARS. We are particularly interested in answering key questions about the disease mechanisms of SARS. For example, are severe outcomes such as acute respiratory distress and mortality entirely caused by the presence of virus, or does the immune system play a role in causing the severe outcomes in some patients? What are the sites and the duration of viral shedding? What is the nature of the immune response? These are central questions to address because they may open up avenues for treatment as well as better preventive strategies.
The identification or development of animal models that mimic human SARS is critical to our understanding of the SARS virus and how it causes disease. Of note, an existing NIAID animal model of a virus infection that causes a disease in mice very similar to SARS has been identified. The relevance of this animal model to SARS will be evaluated and may prove an important tool for defining treatment approaches that involve modulation of the immune system. NIAID will also support the development of other relevant animal models for SARS.
I would be pleased to answer your questions.
Last Revised: May 7, 2003