Institutes and Research Divisions
National Institute of Allergy
and Infectious Diseases

Mission

The National Institute of Allergy and Infectious Diseases (NIAID) conducts and supports research to study the causes of allergic, immunologic, and infectious diseases, and to develop better means of preventing, diagnosing, and treating these illnesses.

Encompassed in the institute mission are studies on the following:

 

Important Events in NIAID History

1948--The National Microbiological Institute was established November 1. The Rocky Mountain Laboratory and the Biologics Control Laboratory, both dating to 1902, were incorporated into the new institute, together with the Division of Infectious Diseases and the Division of Tropical Diseases of NIH.

1951--An institute-supported grants program was initiated, and a branch was established to administer research, training, and fellowship grants. Grant applications were reviewed by the National Advisory Health Council until 1956.

1953--The Clinical Research Branch was renamed the Laboratory of Clinical Investigation.

1955--The National Microbiological Institute became the National Institute of Allergy and Infectious Diseases on December 29. The Biologics Control Laboratory was detached from the institute and expanded to division status within NIH.

1956--The first meeting of the National Advisory Allergy and Infectious Diseases Council was held March 7-8.

1957--The Laboratory of Immunology was established in January to meet the growing need for research on the mechanisms of allergy and immunology.

The Middle America Research Unit was established in the Canal Zone jointly by NIAID and the Walter Reed Army Institute of Research as a temporary field station, made permanent in 1961. Important studies on tropical diseases were conducted there for 15 years. NIAID transferred its portion of the program to the Gorgas Memorial Institute in 1972.

1959--The Laboratory of Parasitic Diseases was established, formerly a part of the Division of Tropical Diseases.

1962--A collaborative research program funded mainly by contracts was established within the institute to plan, coordinate, and direct nationwide projects on infectious diseases, vaccine development, transplantation immunology, research reagents, and antiviral substances.

1967--The Laboratory of Viral Diseases was established.

1968--With the dissolution of NIH's Office of International Research and creation of the Fogarty International Center on July 1, 1968, programs formerly managed by OIR were transferred to NIAID to be administered by the Geographic Medicine Branch. These included 1) the U.S.-Japan Cooperative Medical Science Program, initiated in 1965 by the President and the Japanese Prime Minister to explore the health problems of Asia, and 2) the International Centers for Medical Research and Training, a 1960 congressional initiative to advance the status of U.S. health sciences through international research.

1971--The first seven Allergic Disease Centers were established to translate basic concepts of the biomedical sciences into clinical investigations.

1974--The first centers for the study of sexually transmitted diseases and of influenza were established.

1977--The NIAID Extramural Research Program was reorganized into three areas: Microbiology and Infectious Diseases; Immunology, Allergic and Immunologic Diseases; and Extramural Activities. An intramural Laboratory of Immunogenetics was formed.

1978--The first maximum containment facility (P4) for recombinant DNA research was opened in Frederick, Md. International program project grants and international exploratory/development research grants programs were established. Centers were created for interdisciplinary research on immunologic diseases.

1979--The Office of Recombinant DNA Activities was transferred from the NIGMS to NIAID. The International Collaboration in Infectious Diseases Research Program superseded the International Centers for Medical Research and Training established in 1960.

The Rocky Mountain Laboratory was reorganized into the Laboratory of Persistent Viral Diseases to deal with both host and viral mechanisms leading to slow or persistent viral infections; the Laboratory of Microbial Structure and Function, directed at bacterial diseases, particularly sexually transmitted diseases; and an Epidemiology Branch.

1980--The Laboratory of Immuno-regulation was established to provide a means for applying new knowledge in immunology to the clinical diagnosis and treatment of patients with immunological disorders.

1981--The Laboratory of Molecular Microbiology was created to exploit new techniques in recombinant DNA methodology and other molecular studies to expand the institute's interests in both bacterial and viral pathogenesis and virulence.

1984--The Office of Tropical Medicine and International Research (OTMIR) was established to coordinate NIAID's intramural and extramural research activities in tropical medicine and other international research. OTMIR works with other Federal agencies and international organizations active in these areas.

1985--The Laboratory of Immunopathology was established.

1986--Acquired Immunodeficiency Syndrome (AIDS) Program was established in January to coordinate the institute's extramural research efforts in HIV/AIDS.

1987--The Laboratory of Cellular and Mo-lecular Immunology was established.

1988--The Immunology, Allergic and Immunologic Diseases Program was reorganized and renamed the Allergy, Immunology, and Transplantation Program.

The Office of Recombinant DNA Activities transferred from NIAID to the NIH Office of the Director.

1989--NIAID's programs became divisions: Intramural Research; Microbiology and Infectious Diseases; Allergy, Immunology, and Transplantation; Acquired Immunodeficiency Syndrome; and Extramural Activities.

1990--At Rocky Mountain Laboratories, a section of the Laboratory of Microbial Structure and Function became the Laboratory of Intracellular Parasites. The name of the Laboratory of Pathobiology was changed to the Laboratory of Vectors and Pathogens.

1991--The Laboratory of Host Defenses was established.

1994--The Laboratory of Allergic Diseases was established.

The Office of Research on Minority and Women's Health was created.

At Rocky Mountain Laboratories, the Laboratory of Vectors and Pathogens was renamed the Microscopy Branch.

 

NIAID Legislative Chronology

November 1, 1948--The National Microbiological Institute was established under authority of section 202 of the Public Health Service Act, as implemented by General Circular No. 55, Organization Order No. 20, dated October 8, 1948.

December 29, 1955--NIAID was established (replacing the National Microbiological Institute) under authority of the Omnibus Medical Research Act (P.L. 81-692, 64 Stat. L. 443) as implemented by PHS Briefing Memorandum of November 4, 1955, from the Surgeon General to the Secretary of Health, Education, and Welfare.

November 4, 1988--NIAID was provided with additional authorities under title II of the Health Omnibus Programs Extension Act of 1988 (P.L. 100-607), the first major law to address AIDS research, information, education, and prevention.

August 14, 1991--The PHS act (P.L. 102-96), the "Terry Beirn Community Based AIDS Research Initiative Act of 1991" reauthorized NIAID's Community Programs for Clinical Research on AIDS (CPCRA) for another 5 years.

June 10, 1993--The PHS act was amended by P.L. 103-43, the National Institutes of Health Revitalization Act of 1993. This comprehensive legislation required NIAID to include research on tropical diseases in its mission statement and directed the Secretary, DHHS, to ensure that individuals with expertise in chronic fatigue syndrome or neuromuscular diseases are appointed to appropriate NIH advisory committees.

 

Biographical Sketch of NIAID Director

Anthony S. Fauci, M.D.

Dr. Fauci was born in Brooklyn, New York, in 1940. A graduate of the College of the Holy Cross, he received his M.D. degree from Cornell University Medical College in 1966. After completing an internship and residency at Cornell Medical Center in 1968, he came to the NIH as a clinical associate in the Laboratory of Clinical Investigation, NIAID. In 1977 he was appointed deputy clinical director of the institute.

In 1980 he was appointed chief of the Laboratory of Immunoregulation, a position he still holds. He became NIAID director in November 1984.

He has made many contributions in basic and clinical research in the area of the pathogenesis and treatment of immune-mediated diseases. He pioneered the field of human immuno-regulation by making a number of basic scientific observations that serve as the basis for the current understanding of the regulation of the human immune response. In addition, he is widely recognized for delineating the precise mechanisms whereby immunosuppressive agents modulate the human immune response. He has developed effective therapies for several formerly fatal diseases such as polyarteritis nodosa, Wegener's granulomatosis, and lymphomatoid granulomatosis.

Dr. Fauci has made seminal contributions to the understanding of how the AIDS virus destroys the body’s defenses. He has also delineated the mechanisms of induction of HIV expression by endogenous cytokines. He has been instrumental in developing strategies for the therapy and immune reconstitution of patients with HIV disease.

He continues to devote much of his time to identifying the nature of the immunopatho-genic mechanisms of HIV infection and the scope of the body’s immune responses to the AIDS retrovirus.

During his career at NIH, Dr. Fauci has received numerous honors and awards. Notable are the National Medical Research Award of the National Health Council, the Maxwell Finland Award in Infectious Diseases presented by the National Foundation for Infectious Diseases, the Chiron International Prize for Biomedical Research, the Presidential Award of the New York Academy of Sciences, and the AMA’s William Beaumont Award and Dr. Nathan Davis Award for Outstanding Public Service.

In addition, the Science Citation Index ranked Dr. Fauci as the most-cited author among scientists publishing in AIDS research in the time period 1993-1995.

He is a member of the National Academy of Sciences and the Institute of Medicine, American Federation for Clinical Research, American Society for Clinical Investigation, Association of American Physicians, Infectious Diseases Society of America, American Academy of Allergy, Asthma and Immunology, American Association of Immunologists, American Academy of Arts and Sciences, and American Academy of Microbiology, among others.

He is on the editorial boards of the New England Journal of Medicine, as well as numerous others. He is associate editor of Current Therapy in Internal Medicine, an editor of Harrison’s Principles of Internal Medicine, and author or coauthor of more than 900 scientific publications, including several textbooks.

Director's of NIAID

NameDate of Birth Dates of Office
From
To
Victor H. HaasJan. 6, 1909 Nov. 1, 1948April 1957
Justin M. AndrewsAug. 28, 1902April 1957Oct. 1, 1964
Dorland J. DavisJuly 2, 1911Oct. 1, 1964August 1975
Richard M. KrauseJan. 4, 1925August 1975July 1984
Anthony S. FauciDec. 24, 1940November 1984

 

NIAID Research Program

Investigators at universities, hospitals, and private research institutions throughout the country receive support through grants and contracts administered by the Division of Microbiology and Infectious Diseases; Division of Allergy, Immunology, and Transplantation; and Division of Acquired Immunodeficiency Syndrome.

Division of Microbiology and Infectious Diseases

Viral Diseases. Viruses are the major cause of infectious diseases requiring medical care in the United States. The cost in dollars or in days lost from work is estimated to be in the billions each year. Following an initial infection, which may occur without symptoms, many viruses persist in the body for life and may lead to serious medical problems, including immune complex diseases, degenerative diseases, cancer, heart disease, and ulcers.

NIAID supports basic studies of virus structure, replication, gene regulation and evolution as well as studies in animals and humans that investigate the viral epidemiology, pathogenesis, and host immune response. This research program provides the foundation for the development of vaccines and antiviral therapies.

Respiratory infections are the major cause of acute illness in the U.S. NIAID supports the development and testing of new vaccines against virus-caused respiratory diseases such as influenza and respiratory syncytial and parainfluenza, which cause the majority of croup, bronchitis, and pneumonia in infants and children.

Viral hepatitis caused by hepatitis A, B, C, D, and E is another group of diseases with a major impact on health worldwide. In some parts of the world, hepatitis is the primary cause of liver cancer. Each year in the U.S., more than 600,000 new viral hepatitis infections occur which, when acute, can be debilitating and costly. Chronic disease resulting from infection with hepatitis B, C, and D is an even greater problem. Medical costs for chronic hepatitis are between $1 and $2 billion a year. NIAID-sponsored studies focus on virology, molecular biology, immunology, pathogenesis, development of antivirals, animal model development, natural history, vaccine development and clinical trials. Vaccines have now been licensed for hepatitis A and B.

Diarrheal diseases caused by viruses are particularly a problem among infants in developing countries. Experimental vaccines against rotaviruses--a major cause of infant diarrhea worldwide--have been extensively tested in children and infants. One vaccine developed in NIAID intramural laboratories is expected to be licensed for use in the U.S.

Although there have been reports of possible viral associations in chronic fatigue syndrome (CFS), no specific causative role for any virus has been demonstrated. In order to explore the possible causes of CFS, the institute has funded CFS Cooperative Research Centers to provide a multi-disciplinary approach to CFS research by conducting basic science and clinical investigations on CFS. NIAID also supports scientists who are studying the possible immune system dysfunction, reactivation of latent virus infections, exercise-induced fatigue in CFS patients, as well as other aspects of CFS pathophysiology, and its epidemiology.

Development of Antiviral Drugs. Because many drug sponsors do not have access to comprehensive antiviral screening facilities, NIAID has established screening facilities for the in vitro evaluation of an experimental compound’s activity against the human herpes viruses--herpes simplex virus (HSV) 1 and 2, varicella zoster virus, cytomegalovirus (CMV), and Epstein-Barr virus--and the respiratory viruses--influenza types A and B, respiratory syncytial virus, parainfluenza, measles, and adenovirus. This service is available to any scientist with a potential antiviral compound and an inability to test it. NIAID supports drug evaluation studies, preclinically in animal models of human viral infections and in human clinical trials. Institute-supported investigators participating in the Collaborative Antiviral Study Group are testing drugs for treating herpes encephalitis, neonatal herpes, hantavirus pulmonary syndrome, symptomatic congenital CMV infection, chronic hepatitis B virus infection, flu, and respiratory syncytial virus infection. Other investigators have evaluated interferons for human papilloma infections such as genital warts.

Bacterial Diseases. In the last decade, several bacterial diseases have emerged as new or recurring threats to the health of people in the U.S. and elsewhere, including Lyme disease and tuberculosis (TB).

Lyme disease, first recognized in the early 1980’s in this country, is caused by a bacterium transmitted to humans by certain ticks. It has emerged as a significant problem in the northeast coastal areas, among others. NIAID spearheads NIH studies on Lyme disease, supporting research focusing on pathogenesis, improved therapies, better diagnostic tests, and vaccines.

Tuberculosis, a serious disease once thought to have been conquered in the U.S., is reemerging in certain American cities. TB has a staggering impact worldwide, since one-third of the world’s population is infected with the TB bacterium. Although most people who are infected never develop active TB, those with weakened immune systems--especially those infected with HIV--are particularly vulnerable to active TB disease. Each year 8 million people world-wide develop active TB, and 3 million die.

With appropriate antibiotic therapy, TB usually can be cured. In recent years, however, drug-resistant cases of TB have increased dramatically. Particularly alarming is the increase in the number of persons with multidrug-resistant TB caused by bacterial strains resistant to two or more drugs. Even with treatment, the death rate for multidrug-resistant TB patients is 40 to 60 percent.

As the lead institute responsible for research on TB, NIAID supports basic research into the biology of TB, the development of new tools to diagnose TB, the development of new drugs or ways to deliver standard drugs, clinical trials of anti-TB therapies, and the development of vaccines to prevent it.

NIAID also funds research on leprosy, or Hansen’s disease, which is caused by a mycobacterium. Although treatable today, there are about 1.3 million leprosy patients requiring treatment worldwide, largely in subtropical climates. More than half a million cases are diagnosed each year. Research on atypical mycobacteria, which constitute a diverse and heterogeneous group of acid-fast bacilli that are widespread throughout the environment, is of increasing importance in light of the AIDS epidemic. These organisms rarely cause disease in healthy adults, however, they can cause serious opportunistic infections in people with impaired immune systems.

Cholera is a disease caused by the bacterium Vibrio cholerae. Infection results in severe, dehydrating diarrhea that is particularly dangerous to infants and small children. In 1991 cholera reappeared in the Western hemisphere for the first time in 100 years. The epidemic has spread as far north as Mexico and is a threat to travelers to Central and South America.

In 1992 a new strain of V. cholerae appeared in Asia and in the area of the Bay of Bengal. NIAID supports research aimed at understanding the pathogenesis of the disease, what constitutes protective immunity, and the development of effective vaccines.

Effective antimicrobial agents have significantly reduced the burden of bacterial infections, even though their usefulness is limited by increasing bacterial resistance to antibiotics and in those diseases with an onset and progression so rapid that effective treatment is difficult. NIAID supports the development and testing of bacterial vaccines for Hemophilus influenzae type b, Streptococcus pneumoniae, all causes of meningitis; pertussis (whooping cough); cholera; shigella; and typhoid fever.

Hospital-associated, or nosocomial, infections have emerged in recent years as a significant health problem and cause of increased morbidity and mortality. They directly contribute to rising health care costs. An estimated 2 million hospital-associated infections occur in the U.S. each year, at a cost of more than $3 billion.

Gram-negative sepsis following surgery or trauma remains the most serious threat to patients, with mortality rates ranging from 25 to 40 percent if sepsis occurs. NIAID supports studies on immune mechanisms--cellular and humoral--that protect healthy people against normal microbial flora commonly encountered every day. Another focus is the study of disturbances in resistance mechanisms in hospitalized or immunocompromised patients. Gram-negative bacteria from the gastrointestinal tract are the primary etiologic agents and many have become resistant to antibiotics.

Hospital acquisition and transmission of methicillin-resistant staphylococci, Candida, enterococci, and antibiotic-resistant gram-negative bacteria are important areas of investigation.

The interplay of bacterial toxins such as lipopolysaccharide and staphylococcal toxic shock toxin with host serum and cell components can result in fever, shock, and death. NIAID is investigating the underlying mechanisms of shock and its control and prevention.

 

NIAID Appropriations -- Grants and Direct Operations
[Amounts in thousands of dollars]

Fiscal
Year
Total Grants
$
Direct Operations
$
Total
$
19542,0673,6715,738
19552,2273,9536,180
19562,2275,5487,775
19578,1825,11713,299
195811,591 5,80917,400
195917,0916,98024,071
196026,2807,77434,054
196135,1418,85944,000
1962 43,900 12,19156,091
196349,25616,88666,142
196451,17517,54868,723
196551,28818,55969,847
196656,06221,92577,987
196764,80925,86190,670
196866,45427,96894,422
196966,086 28,75496,840
197074,24829,446103,694
197170,28532,083102,368
197275,48633,689109,175
197378,55734,857113,414
197476,90839,092114,000
197578,09341,359119,452
197682,39044,462126,852
197790,92850,272141,200
1978106,31856,023162,341
1979130,34060,988191,328
1980153,01062,354215,364
1981168,15463,923232,077
1982 169,69066,205235,895
1983199,28979,840279,129
1984226,40793,189319,596
1985267,940102,107370,047
1986266,928100,214367,142
1987367,076178,357545,433
1988458,445180,076638,521
1989517,159226,993744,152
1990568,986263,991832,977
1991606,138300,113906,251
1992643,115316,799959,914
1993685,661298,566984,227
1994716,336347,3601,063,696
1995733,935358,5721,092,507
1996781,340365,1271,171,160

 

Fungal Diseases. Severe, sometimes life-threatening systemic infections caused by fungal organisms have long been recognized in all age groups and in all parts of the U.S. Treatment requires prolonged administration of relatively toxic drugs and is sometimes ineffective, even in the otherwise healthy patient. Fungal infections are increasingly recognized as a major cause of morbidity and mortality in patients with impaired immune defenses. NIAID supports research on medically important fungi such as Coccidioides immitis, Histoplasma capsulatum, Blastomyces dermatitidis, Cryptococcus neoformans, Candida albicans, and Aspergillus fumigatus.

Antimicrobial Drug Development. As promising new antibacterial and antifungal agents are developed, they must be critically evaluated for safety and efficacy in humans. NIAID selects for trial licensed and unlicensed drugs that the pharmaceutical industry is unlikely to test further in humans, even though the drugs may show considerable clinical promise. Controlled, prospective, and multicentered studies are designed to compare efficacy, safety, duration, and costs with standard chemotherapeutic agents. Currently, the institute supports trials of new systemic antifungal agents, an improved treatment regimen for urinary tract infections in women, antibiotic prophylaxis of respiratory infections in children with cystic fibrosis, and together with NICHD, an antibiotic trial for vaginal infections in pregnant women.

Sexually Transmitted Diseases (STD). A dramatic increase in the number of new cases of STDs has occurred over the past 50 years in the United States. Gonorrhea, syphilis, genital herpes, genital warts, chlamydial infections, and pelvic inflammatory disease (PID) take an increasingly large toll emotionally, physically, and economically. Each year in the U.S. there are approximately 4 million new cases of chlamydia, 1 million new cases of gonorrhea and 1 million new cases of PID. Thirty million Americans are estimated to have genital herpes, and 24-40 million are thought to be infected with human papillomavirus (HPV), several types of which are associated with development of cervical cancer.

STDs often have long-term, devastating consequences--particularly for women and children. Infertility, ectopic pregnancy, cervical cancer, increased risk of infection with HIV, fetal death, low birth weight, and congenital infections resulting in permanent physical and mental damage to infants, can result from STDs. In 1995 economic costs associated with PID alone were estimated to exceed $6 billion.

Current research priorities and initiatives focus on vaccine development, the sequelae of STDs in women, behavioral research, HPV, genital ulcer disease, the development of rapid, inexpensive diagnostics, and the development of topical microbicides.

NIAID conducts and supports basic research necessary to develop vaccines against gonorrhea, chlamydial infections, and syphilis.

Because of the severe and disproportionate impact of STDs on health of women and infants, NIAID seeks to develop and evaluate interventions to reduce the incidence and severity of complications of PID, such as infertility, ectopic (tubal) pregnancy, and chronic pelvic pain syndromes. Furthermore, because STDs are preventable causes of adverse outcomes of pregnancy such as fetal wastage, low birth weight, and congenital infections, this area is also a priority.

In recognition of the critical interplay between behavioral and biomedical risk factors for STDs, NIAID is developing a program in integrated, intervention-oriented behavioral research for the prevention and control of STDs.

Studies of the pathogenesis and natural history of HPV are important areas of research. The role of HPV in development of cervical dysplasia and malignancy, HPV’s role in transmission of HIV, development of animal models of genital HPV infection, and improved methods for detection and management of HPV infection are among the research areas of interest to NIAID.

The expansion of research on the pathogenesis and natural history of genital ulcer disease and on the interrelationship between these diseases and HIV is of high priority. Research on chancroid, syphilis, and genital herpes is being emphasized.

Parasitic Diseases. Parasitic diseases, a world health problem, affect billions of people and are responsible for millions of deaths annually. While their principal health and economic impact is felt primarily in poor and developing countries, many parasitic infections remain endemic within the United States and can present a threat to individuals with immature or compromised immune systems or in situations where normal sanitation procedures break down. In addition, increased foreign travel by U.S. citizens as well as immigration to the United States allows importation of so-called “exotic” parasites from other countries.

Several unicellular protozoa and multicellular helminths cause parasitic disease. Goals of NIAID-sponsored studies on the immunology of parasitic diseases include development of effective vaccines against malaria, schistosomiasis, leishmaniasis, and others; the intervention in the host response to prevent immunologically mediated disease processes; and the development or improvement of immunodiagnostic procedures. NIAID also supports basic research on the biochemistry and molecular biology of parasites to develop new chemotherapeutic agents or improve the efficacy of existing drugs. Development of drug resistance is a rapidly increasing problem, particularly in malaria. Application of modern biochemical and molecular technology to determine how resistance develops may reveal ways to reverse the phenomenon.

NIAID supports Tropical Disease Research Units at domestic institutions to provide a stable environment for research on parasitic diseases. These programs apply relevant and innovative biomedical technology to develop new approaches to control parasitic diseases.

Vaccine Development. Vaccines have virtually eliminated once common killers such as diphtheria, tetanus, and polio in the U.S. Nearly 25 major human diseases caused by infectious agents are preventable or controllable through vaccine use. Despite this success, both new and old infectious diseases continue to threaten the health of people around the world.

The aim of the NIAID vaccine program is to capitalize on the extraordinary advances in molecular biology and immunology in order to improve the safety, effectiveness, and efficiency of existing vaccines and enhance the development of new vaccines. This is also the goal of the Children’s Vaccine Initiative, a global project of which NIAID is an integral part.

As the lead PHS agency for vaccine research, NIAID coordinates a comprehensive program among scientists in government, industry, and academic settings. Vaccine research is conducted by NIAID scientists as well as by institute-supported investigators at research institutions, including six Vaccine Treatment and Evaluation Units. The units conduct clinical trials of candidate vaccines to determine whether they are safe, immunogenic (capable of stimulating an immune response), and effective.

Research on HIV vaccines is supported by NIAID’s Division of AIDS.

International Research

The institute’s international research activities involve grants, contracts and intramural projects to promote scientific research on tropical and other diseases of great importance to the health of people in developing and developed countries of the world.

Immediate aims are to improve means for diagnosing, treating, and controlling these diseases with the ultimate goal of disease prevention. For example, the U.S.-Japan Cooperative Medical Science Program, organized in 1965, provides an opportunity for American and Japanese scientists to cooperate in studying 10 disease-related areas of importance to the health of Asian people.

In September 1979, the International Collaboration in Infectious Diseases Research Program replaced the International Centers for Medical Research and Training which had been operational since 1960. Under the new program, research centers are established in tropical countries through multidisciplinary program project grants awarded to U.S. institutions. The program is designed to promote true collaboration and scientific exchange between U.S. scientists and their overseas counterparts. The program addresses infectious diseases of health importance to the host country. In 1991 NIAID established Tropical Medicine Research Centers to provide overseas facilities for the study of tropical diseases within endemic areas.

Other international activities include the NIAID-USAID Middle East Regional Cooperation Program, carried out through Jordan, Morocco, Lebanon, Tunisia, and Israel, to study leishmaniasis and hydatid disease. NIAID also coordinates studies on the immunology of infectious diseases as part of the Indo-U.S. Science and Technology Initiative.

Division of Allergy, Immunology and Transplantation

This division focuses on the immune system as it functions in the maintenance of health and as it malfunctions in the production of disease. It encompasses basic and clinical research.

Basic research is supported in 1) immuno-biology and immunochemistry and 2) immunogenetics and transplantation immunology. Clinical research is supported in asthma and allergic diseases, and immunologic diseases and immunopathology. NIAID's approach integrates the basic science disciplines with relevant clinical specialties.

Basic Immunology. The biology and chemistry of the immune system and its products are the concerns of this program area. Immunobiologic studies focus on the origin, maturation, and interactions of the immune system's major cells, lymphokines, and other substances produced by theses and other cells that mediate immune reactions. Studies include the mechanisms responsible for the induction and regulation of the immune response. Immunochemical research encompasses the delineation of the chemical structure and function of antigens and antibodies; the chemical basis of immunologic specificity; the regulation of immunoglobulin synthesis; and the mechanisms of antigen-antibody reaction.

Research projects in this area are designed to:

Genetics and Transplantation. The pri-mary goals of genetics and transplantation research are to:

By supporting the acquisition, characterization and distribution of tissue typing reagents and the evaluation and improvement of tissue typing methodologies, the program facilitates the matching of donors and recipients for transplants. It also supports studies on the relationship of the human major histocompatibility complex (MHC) HLA antigens to disease susceptibility.

Research projects in this area are designed to:

Identification and Acquisition of Reagents. NIAID contracts serve as sources of standard reagents to identify cell surface antigens both within and outside of the major histocompatibility complex that play a role in immune response.

Some of these reagents are available for use in workshops or similar large-scale studies.

The institute also is a primary source of standard reagents for distribution and analyses for basic immunogenetic studies of murine transplantation antigens.

Transplantation. Program projects in transplantation immunology, located at major transplant centers, are currently funded by NIAID to facilitate the rapid translation of basic immunologic discoveries into clinical use. The centers carry out basic and clinical research pertinent to mechanisms of rejection, organ availability and preservation, and management of rejection.

National Cooperative Clinical Trial in Transplantation. NIAID established this trial to expedite the evaluation of new treatment modalities to prevent kidney graft rejection. Multicenter clinical trials to assess thepotential efficacy of various therapies are conducted at eight kidney transplant units throughout the U.S.

Asthma, Allergy and Inflammation. More than 50 million Americans suffer from allergic diseases including asthma. NIAID supports studies encompassing the cause, pathogenesis, diagnosis, prevention, and treatment of allergic diseases. Various types of allergic problems under investigation include: immediate type hypersensitivity and its disorders, including asthma, allergic rhinitis, atopic dermatitis, urticaria and angioedema; allergic reactions and disorders caused by insect bites and stings, foods, airborne allergens, and infectious agents; manifestations of delayed hypersensitivity and contact dermatitis; and the mechanisms of drug reactions and chemical sensitization. Studies also include structure of the antibodies, particularly IgE, and the chemical mediators released by the interaction of antigen and antibody with target cells; the isolation and chemical characterization of the active fractions of allergenic agents; and the therapy and prevention of allergic disorders and hypersensitivity reactions by immunotherapy with specific antigens or drugs.

Asthma, Allergic and Immunologic Disease Cooperative Research Centers. A network of cooperative research centers represents an effort to integrate the basic concepts of immunology, genetics, biochemistry, and pharmacology into clinical investigations of patients with asthma, allergic and immunologic diseases. The program encourages collaboration between basic and clinical scientists, provides a research environment for such interactions, and implements clinical application of adequately tested research findings and procedures. It is believed that this will lead to an understanding of the pathophysiologic, biochemical, and immunologic mechanisms of these disorders.

National Cooperative Inner-City Asthma Study. NIAID established this study to assess the factors contributing to the increased morbidity and mortality from asthma among children residing in urban environments, and to develop and evaluate a comprehensive therapeutic, educational, and environmental intervention program designed around those contributing factors. Seven sites in six cities nationwide are participating in this cooperative study.

Clinical Immunology. Investigations of underlying mechanisms of disease and applications of basic knowledge to the cause, prevention, and management of immunologic disorders are approached from either of two disciplines--clinical immunology or immunopathology. Studies of clinical immunology involve acquired and inherited diseases associated with dysfunctions of the immune system, whereas the immunopathology studies encompass genetics, cytology, biochemistry, pathology, and pharmacology of the immune system.

Areas under investigation include:

DAIT supports program projects in mechanisms of immunologic diseases and autoimmunity aimed at increasing the understanding of pathophysiologic processes of immune-mediated diseases and the development of improved methods of diagnosis, treatment and prevention of disorders of the immune system.

Division of AIDS

The mission of the Division of AIDS is to increase basic knowledge of the pathogenesis, natural history, and transmission of HIV disease, and to promote progress in its detection, treatment, and prevention.

DAIDS accomplishes this mission by planning, implementing, and evaluating programs in:

In accord with this mission, the division's efforts are organized around five broad scientific areas: 1) pathogenesis, 2) epidemiology and natural history, 3) therapeutics research and development, 4) vaccine and prevention research and development, and 5) pediatric disease.

HIV Pathogenesis. Research on the pathogenesis of HIV infection will advance the understanding of the biological causes of HIV-related disease and serve as a foundation for advancing treatment and prevention.

Investigator-initiated research and the traditional research grant are the foundation of the division's activity in this area. Important research gaps are identified by division staff in concert with investigators and advisory committees.

Other key NIAID resources for the study of pathogenesis include:

Epidemiology and Natural History. The division's goals in the area of epidemiology and natural history are to foster population-based research that will advance the understanding of the biology and clinical course of HIV infection and serve as a foundation for advancing treatment and prevention.

The division oversees several large longitudinal cohort studies that conduct multidisciplinary research involving specific populations of individuals infected with or at significant risk of infection with HIV. These include:

In addition to collecting clinical data obtained at serial examinations and interviews, all of these studies are linked to a DAIDS-supported repository that stores a variety of serially collected biological specimens from participants and subsequently retrieves them for use in experiments conducted by investigators around the world. These studies therefore represent a powerful investigative tool for basic and applied research in pathogenesis, diagnosis, behavior, treatment, and prevention.

Vaccine and Prevention Research and Development. Development and testing of vaccines and other biomedical interventions such as drugs and microbicides to prevent HIV disease is a key role of DAIDS-funded research.

NIAID's efforts in vaccine research and development are built on a strong foundation of investigator-initiated research in basic virology, immunology, and microbiology. In addition, the division uses a number of specific applied resources to advance its objectives. These include:

Therapeutics Research and Development. The division’s goal in therapeutics is to foster the discovery and development of interventions that will improve the quality and duration of life of HIV-infected individuals.

NIAID devotes substantial resources to the discovery stage of therapeutics research, attempting to focus resources on areas of promise that are receiving insufficient attention from the private sector. The effort begins with a strong commitment to basic research in microbiology and pathogenesis. Upon this are built programs of targeted drug discovery with the National Cooperative Drug Discovery Groups (NCDDGs) for HIV and opportunistic infections (OIs) at the center. These consortia of academia, industry, and government investigators work collaboratively on focused “gap” areas of targeted drug discovery. Small portfolios of highly applied traditional investigator-initiated research round out this effort.

NIAID’s preclinical development resources are limited in scope to those necessary to ensure that the national effort has the capability to carry out specific rate-limiting developmental steps involving selected highly promising candidate agents that lack a private sponsor with sufficient resources or commitment. These “gap-filling” resources include capabilities for 1) chemical resynthesis; 2) analytical chemistry and quality control; 3) dosage form development and manufacturing; 4) small and large animal toxicology; and 5) in vitro screening and animal model efficacy studies.

In addition, the Special Program for Innovative Research on AIDS Treatment (SPIRAT) fosters coordinated and interdependent basic and clinical research between current HIV pathobiology and clinical evaluation of novel therapeutic strategies.

NIAID conducts clinical trials of new therapeutics in three networks:

Pediatric Disease. DAIDS is working to identify and support the development of improved interventions to prevent and treat HIV infection and its sequelae in infants, children, and adolescents. DAIDS’ goals in pediatric disease include: 1) preventing perinatal HIV transmission to infants and HIV transmission to adolescents and children; 2) developing technology for the early identification and diagnosis of HIV-infected infants; and 3) developing and optimizing therapies for HIV and its sequelae in infants, children, and adolescents.

Specific resources related to pediatric disease include:

Division of Intramural Research

The institute’s Division of Intramural Research (DIR) consists of 16 laboratories, of which 13 are on the Bethesda campus and at off-campus sites in Frederick and Rockville, Md., and 3 are located at the Rocky Mountain Laboratories in Hamilton, Mont. Scientists in these laboratories conduct basic and applied research in immunologic, allergic, and infectious diseases and related clinical disorders. Considerable effort is devoted toward vaccine development and the understanding of the immune system’s ability to react to certain antigens.

The scope of laboratory investigations includes the disciplines of virology, parasitology, mycology, microbiology, biochemistry, immunology, immunopathology and immunogenetics. Additionally, the DIR supports a 52-bed inpatient service and an outpatient facility located in the Clinical Center on the NIH campus. Patients with a variety of diseases under study, including AIDS, vasculitis, immunodeficiencies, host defense defects, unusual fungal infections, asthma, allergies, various parasitic diseases and disorders of inflammation, are seen. Frequently these patients participate in new and exciting treatment or diagnostic procedures derived from ongoing laboratory research efforts.

Successful vaccines or therapies for infectious diseases derive from a myriad of research activities on the disease agent as well as interactions of the agent with the host. The human immunodeficiency virus associated with AIDS is a major challenge to DIR scientists and physicians. The development of suitable laboratory animal models is critical to developing therapeutic strategies and vaccines for AIDS.

DIR scientists are studying the immunopathogenesis of HIV infection as well as the immune response to the virus. Cytokines have been shown to induce the expression of HIV in latently or chronically infected cell lines,thus providing tools for understanding the mechanisms of the insidious progression of immunosuppression in HIV-infected individuals.

In addition, NIAID researchers are exploring the many components of HIV disease, including phases of immune system activation and suppression. In studying the dissemination of HIV to lymphoid tissues in the body such as the lymph nodes and spleen, the investigators have found that HIV is active within these tissues from the earliest stages of HIV infection. This finding provides a scientific rationale for early treatment when safer and more effective antiretroviral drugs become available. DIR investigators have conducted intensive studies of antiretroviral and immuno-modulator therapies. Clinical trials of a number of therapies, including use of IL-2 to maintain CD4 levels, are under way.

NIAID intramural scientists are working to develop and test vaccines against a number of infectious agents such as viruses causing AIDS, dengue fever, diarrhea in infants, and pneumonia and croup in infants and young children. Bacterial agents that cause sexually transmitted diseases such as chlamydia and gonorrhea, and Lyme disease are under active investigation. Approaches to the development of a vaccine against malaria are being explored. Promising new vaccine candidates are tested in the clinical setting for safety, immunogenicity, and if warranted, efficacy.

Basic immunologic studies are aimed at defining the components and mechanisms of action of the humoral and cellular responses. Receptors on T lymphocytes and peptides linked to the surface of antigen presenting cells are being defined. Information derived from these studies may allow the design of peptides that can inhibit specific immune responses and may have great importance in controlling the rejection associated with transplantation.

DIR researchers are carrying out intensive studies of the role of newly discovered cytokines in T-cell differentiation. Researchers have found that interleukin 12 (IL-12) plays a pivotal role in the induction of T-cell responses, which are important for the control of intracellular infections.

B lymphocytes, critical components of the immune response and responsible for antibody responses, are being dissected for studies of structure and function. Among the studies being conducted are those related to the control of B-cell immunoglobulin class switching. It has been shown, for instance, that IL-4 and INF-gamma reciprocally regulate IgG1 and IgE responses in mouse systems. In addition, the role of TGF-beta in IgA class-switching has been clarified. These studies are important in the design of future vaccines that can enhance the production of certain forms of antibody.

Inflammation is an important aspect of immunity. One of the important mediators of inflammation is a series of nine proteins called the complement system. NIAID scientists identified a new protein present in large concentrations in plasma of humans. The new protein binds to the fourth protein of the complement cascade where it acts as an inhibitor of this important inflammation-producing system. The inhibitor also interacts with the kinin-generating and coagulation systems. Certain patients with unusual swelling disorders have an abnormality in the degradation of this protein, and thus the protein may be very important in certain swelling disorders.

The first evidence that an immunodeficiency can be treated with a naturally occurring product of lymphocytes was recently demonstrated by DIR scientists. Chronic granulomatous disease of childhood (CGD), a disease in which there is a defect in the ability of the scavenger cells of the immune system to produce hydrogen peroxide, renders the patient susceptible to certain infectious agents. A multicenter clinical trial of interferon gammain patients with CGD followed in vitro studies which demonstrated the effectiveness of interferon gamma in correcting the defect in phagocytes from these patients. Interferon gamma was shown to significantly reduce the number of serious infections in CGD patients. These studies led to FDA approval of this drug for use in CGD.

Studies of the immune response to the causative agent of leishmaniasis have demonstrated that immunity to the parasite is not only to a specific antigen, but also to a certain immune cell. DIR scientists have shown that the outcome of leishmaniasis depends on whether the animal develops a TH1 response with T cells that produce IL-2 and IFN-gamma, or a TH2 response with T cells that produce IL-4 and IL-5. In the former case, granulomas develop that wall off and kill leishmania in the latter case, the infection is disseminated.

Studies of allergy are carried out by investigators working in basic immunology laboratories as well as by clinical and laboratory investigators working within the Asthma and Allergic Diseases Center. One effort has been the study of IgE antibody which mediates allergic responses by causing mast cells to release mediators of allergic responses. IL-4, produced by T cells, is essential for production of IgE in mice. Administration of IL-4 to mice prevented increases in IgE antibodies normally observed in immune responses to certain antigens. In other studies, DIR scientists have developed a “knockout” mouse that lacks receptors for IgE antibodies on the surface of mast cells. These mice will facilitate a better understanding of the role of IgE responses in the production of allergic symptoms.

Studies of the mechanisms of allergies have emphasized work on mast cells. Mast cells are the central cells of allergic responses because when activated by an allergen and IgE they release the mediators of allergy. New techniques have been developed in order to grow human mast cells in culture, an advancement that will enable more detailed investigations into their biology. An improved approach to the treatment of asthma has been devised by DIR researchers. The concept is based upon separating bronchodilators from agents that act to reverse specific processes in the pathogenesis of asthma. Specifically, patients are placed on symptomatic therapy in order to permit the more specific therapy to act. Inhaled cromolyn, systemic corticosteroids and immunotherapy are employed as specific agents while beta adrenergic agonists, theophylline, and atropine are symptomatic agents. This approach is gaining increased acceptance and should improve long-term treatment of asthma.