The past year has been a time of considerable accomplishment at the
National Institute of Allergy and Infectious Diseases (NIAID), as NIAID-supported
scientists made major strides in understanding, preventing and treating important
infectious and immunologic diseases that threaten the health of people in the United
States and abroad.
NIAID-supported investigators reported significant new advances in
fighting several of the leading reportable infectious diseases in the United States,
including the acquired immunodeficiency syndrome (AIDS), chlamydia and other
sexually transmitted diseases, tuberculosis, and Lyme disease. Significant progress was
made in the research effort against infectious killers of children, such as diarrheal
diseases. Other findings suggested new approaches for treating autoimmune diseases
such as multiple sclerosis.
Each of these recent accomplishments was facilitated by knowledge
gleaned through basic research. For example, the fundamental discovery in the 1970s
of how the immune system distinguishes "self" from "non-self," for which two long-time
NIAID grantees were awarded the 1996 Nobel Prize for Physiology or Medicine,
influenced many of the advances I will discuss.
The translation of basic research findings into practical applications has
been particularly noteworthy in the fight against the human immunodeficiency virus
(HIV), the virus that causes AIDS. Fundamental research into the structure and
function of the HIV protease enzyme led to the development of a powerful new class of
anti-HIV medications that block this enzyme, and hence the replication of the virus.
Three of these drugs, called protease inhibitors, were recently approved for marketing in
the United States; others are in late stages of clinical testing. Protease inhibitors are
now widely prescribed as part of combination treatment regimens for HIV-infected
people, and in some patients have controlled the replication of HIV to a degree not
previously possible. NIAID currently is conducting clinical trials to determine how
best to use protease inhibitors and whether their significant short-term benefits are
sustainable for prolonged periods without prohibitive toxicities or the widespread
development of drug resistance.
In another major development in AIDS research, two separate fields of
scientific inquiry converged to provide long-sought information on the HIV disease
process and important new targets for therapies. One group of researchers demonstrated
that certain immune signalling molecules called chemokines, normally secreted as part
of the body's inflammatory response, can suppress certain strains of HIV. Other
investigators identified molecules on the surfaces of immune system cells that play key
roles in enabling different strains of HIV to infect the cells.
It soon became clear that these findings were related and complementary.
In important instances, chemokines suppress HIV because they bind to the same cell
surface molecules needed by the virus for entry. These discoveries suggest that it might
be possible to treat HIV infection with drugs that block these cell surface molecules, or
to prevent infection with vaccines that elicit antibodies that inhibit the binding of HIV
to the molecules. Scientists around the world are now pursuing these and related
approaches, building on the exceptional leads provided by NIAID-supported
The development of an HIV vaccine remains an important goal of the
Institute, one we are pursuing with a two-pronged strategy of basic and applied
research. Basic researchers are uncovering important clues about the specific immune
responses that might protect an individual from HIV infection or disease progression.
Parallel with basic research efforts, the Institute continues to test candidate vaccine
products in small-scale trials around the world. Since 1988 more than 2,300 non-HIV
infected adult volunteers have enrolled in approximately 30 phase I and II vaccine trials
conducted in the United States by NIAID's AIDS Vaccine Evaluation Group (AVEG).
These trials have involved 16 experimental vaccines, 12 immune-stimulating substances
called adjuvants and a variety of delivery vehicles and routes, dosages and
Early clinical studies of experimental HIV vaccines focused on products
based on a single protein from the envelope of HIV. These have given way to more
complex strategies, including a two-step approach in which a person is injected with a
harmless virus genetically engineered to make HIV proteins, and later given a booster
shot of an HIV-derived protein. This so-called "prime-boost" strategy has shown
promise in non-human primate models of AIDS, protecting a significant proportion of
animals. Small-scale studies in human volunteers suggest that the approach is safe and
can stimulate anti-HIV antibodies, as well as cytotoxic T cells, which kill HIV-infected
The HIV epidemic is inextricably linked to other sexually transmitted
diseases (STDs). HIV and other STDs share a common mode of transmission, and
people with STDs are more likely to transmit HIV or become infected with HIV than
people without STDs. It is often underappreciated, however, that STDs are an
enormous problem in their own right; they comprise a "hidden epidemic" that the
Institute of Medicine recently addressed in a lengthy report. Altogether, more than 12
million Americans acquire a sexually transmitted disease (STD) other than HIV each
year, at a total cost to the Nation that exceeds $10 billion (Institute of Medicine, 1997).
In addition to their huge economic burden, STDs can have devastating health
consequences. For example, hepatitis B virus is a leading cause of liver cancer, and
certain types of human papillomavirus account for nearly all cancers of the cervix,
vagina, vulva, anus and penis. Untreated chlamydial and gonorrheal infections
frequently lead to pelvic inflammatory disease (PID), which in turn can result in
life-threatening tubal pregnancies and scarring of a woman's fallopian tubes leading to
The NIAID has addressed the challenges posed by STDs with a
multidisciplinary research strategy encompassing basic, applied and behavioral
research. For example, the Institute is developing topical microbicides, substances that
a woman can use in her vagina before intercourse to prevent the transmission of
sexually transmitted microbes, including HIV. Several promising microbicides are in
various stages of pre-clinical and clinical development. NIAID-supported scientists
also are developing better diagnostic tests to help clinicians detect and treat
asymptomatic STDs before they cause serious health problems. Sensitive, non-invasive
urine tests for chlamydia and gonorrhea hold particular promise for detecting
both symptomatic and asymptomatic cases of these diseases, especially in the context of
large-scale screening programs. Screening for asymptomatic STDs can have a notable
effect: a recent NIAID-funded trial demonstrated that women screened and treated for
asymptomatic chlamydial infection were 60 percent less likely than unscreened women
to develop pelvic inflammatory disease.
Dehydration due to diarrheal diseases is a leading causes of death
worldwide, particularly among children. Rotaviruses cause 35 to 50 percent of the
world's severe diarrhea cases in infants and young children, resulting in more than
800,000 deaths annually. In the United States, more than 1 million cases of rotaviral
diarrhea and 50,000 hospitalizations occur each year. Because of a lack of a specific
drug to treat this condition, scientists at NIAID designed and tested a vaccine that
combines human and animal rotavirus genes. In large-scale clinical trials, this vaccine
has been found safe, with only mild side effects, and effective 80 to 90 percent of the
time. The vaccine is now nearing licensure and promises to have a major impact on the
health of the world's children. The successful development of this vaccine exemplifies
the synergy between basic and applied research, as well as the fruitful collaborations
that are possible between the private and public sectors.
NIAID-funded investigators are now working on the vaccines of the
future: "naked DNA" vaccines, which contain the gene or genes for the antigenic
portion of a pathogen, injected directly into the muscle of a patient. These vaccines
have many potential advantages over conventional vaccines, including greater purity
and stability, economy and ease of purification, and relative safety in
immunocompromised individuals. The use of naked DNA vaccines may offer a way to
develop a better childhood vaccine that is easily delivered and provides durable
immunity against multiple pathogens without requiring refrigeration.
Recent studies in mice show the feasibility of designing naked DNA
vaccines to prevent tuberculosis. Naked DNA vaccines also have shown promise for
many other conditions. For instance, a naked DNA influenza vaccine has protected
laboratory animals from multiple strains of influenza virus. Further development of this
approach may one day reduce the need to prepare new vaccines each year to prevent
epidemics caused by different strains of influenza virus.
Lyme disease, first recognized in the 1970s, is the most common
vector-borne infection in the United States. Much of the progress in understanding this
condition has been facilitated by NIAID-supported discoveries. An NIAID investigator
identified the causative bacterium, and NIAID-supported research subsequently
revealed how the bacterium is transmitted and causes disease. NIAID-supported
researchers also identified the bacterial surface antigens on which improved diagnostic
tests and experimental vaccines are based.
Although most patients diagnosed with Lyme disease are successfully
treated soon after infection, a small proportion develop a chronic condition called
Post-Lyme Disease Syndrome, characterized by persistent musculoskeletal and
peripheral nerve pain, fatigue and memory impairment. Scientists have speculated that
the syndrome may be caused by ongoing infection with the Lyme bacterium or another
tick-borne pathogen, or perhaps by persistent inflammatory or immune responses;
however, the precise pathogenesis is unclear. Recently, the Institute launched a
five-year initiative to study the pathogenesis and treatment of this elusive syndrome.
The Institute also continues its concerted efforts to unravel the mysteries of
the chronic fatigue syndrome (CFS), a debilitating illness for which a definitive cause
or treatment remains elusive. In a recent NIAID-supported study, investigators found
that therapy for abnormally low blood pressure alleviated the symptoms of chronic
fatigue syndrome (CFS) in 9 out of 23 patients. This finding has led to an
NIAID-supported clinical trial involving treatment of CFS with a specific drug typically
used to treat hypotension.
Autoimmune diseases such as multiple sclerosis (MS) occur in 5 percent of
adults in the United States, two-thirds of them female. MS is the most common
progressive neurologic disease of young Americans, affecting an estimated 250,000 to
350,000 people in the United States. Using a mouse model of multiple sclerosis (MS)
called experimental allergic encephalomyelitis (EAE), NIAID-supported scientists have
discovered that a specific interaction between two types of critical immune cells is
associated with the symptoms of EAE and MS. Moreover, they found that blocking
this interaction prevented EAE in mice and dramatically improved symptoms in mice
that already had EAE. These findings suggest a potential new approach for alleviating
symptoms of MS in people.
As the above examples illustrate, new insights in fields such as
immunology and microbiology, the cornerstones of the NIAID research effort for nearly
fifty years, continue to drive the development of new treatments, vaccines, diagnostic
tests and other technologies crucial to the health of the Nation. With a continued
commitment to basic and applied research, even greater accomplishments can be
expected as we approach the 21st century.