Sarah Goodwin

Kathi Ovnic
Holly Korschun
October 14, 1999

With the dedication of its new Vaccine Research Building on October 14, Emory University underscores its commitment to world leadership in the fight to eliminate or control the deadly infectious diseases that continue to plague millions of individuals around the globe. The Emory Vaccine Research Center assembles a group of the nation’s most respected immunologists and virologists in one of the largest centers ever created to forge new vaccine strategies.
To most young adults in America, diseases like smallpox, polio and yellow fever sound like exotic diseases of a time long past. These crippling afflictions are no longer a threat in this country because vaccines were developed to prevent them.

A number of diseases remain, however, for which there are no effective restraints in many areas of the world.
"The idea of the Vaccine Center is to create new technologies that will make our most challenging problems such as AIDS, malaria, tuberculosis, influenza and respiratory viruses a thing of the past," says Rafi Ahmed, Ph.D., director of the Center and the Georgia Research Alliance Eminent Scholar in Vaccine Research. "Vaccines are also the most cost-effective way to prevent these disease," he says. Dr. Ahmed is an internationally recognized scientist in viral pathogenesis and immunity, and is one of the world’s leading experts on T-cell memory.

The new 75,000-square-foot, four-story Vaccine Research Building adjoins the main building of the Yerkes Research Center adjacent to the Emory University campus. Consisting of three above-ground levels and one below-ground level, the building houses investigators in 23 state-of-the-art laboratories, as well as contemporary offices and meeting facilities. Long recognized as one of the leading centers for biomedical and biobehavioral research with non-human primates, the Yerkes Center in recent years has expanded to include a broad range of scientific research from molecular and cellular studies to investigations of cultural and social behavior.

In addition to the investigators within its new building, the Vaccine Research Center functions as an interdisciplinary "center without walls," providing a focus for research in immunology and vaccines for investigators throughout Emory University’s Woodruff Health Sciences Center and for collaborative scientists at the Centers for Disease Control and Prevention (CDC), the Carter Center and nearby academic institutions.

"Not only does this building house a group of the world’s pre-eminent microbiologists and virologists, it also creates a unique opportunity for collaboration that will allow these investigators to make discoveries that would not be possible in individual, isolated laboratories," said Michael M.E. Johns, M.D., Executive Vice President for Health Affairs and Director of the Robert W. Woodruff Health Sciences Center. "These scientists have come to Emory from leading institutions throughout the country knowing that, along with their fellow investigators, they can make a significant worldwide impact on disease."

In 1997 the National Institutes of Health named the development of a safe and effective AIDS vaccine "a global public health imperative," and President Clinton challenged the scientific community to develop an AIDS vaccine within ten years. Most scientists agree than global control of HIV, which now affects 34 million people worldwide, will be achieved only through widespread availability of a safe, effective, inexpensive vaccine. In 1998 the National Institutes of Health designated and funded the Emory/Atlanta Center for AIDS Research (CFAR) as an official NIH CFAR site. More than 100 Emory investigators, along with their collaborators at other institutions, are conducting research related to the prevention and treatment of AIDS, including vaccines.

Mark Feinberg, M.D., Ph.D., served as medical officer for the Office of AIDS Research at the NIH before joining Emory in 1998 as associate director of the Emory/Atlanta CFAR and as associate professor of medicine and microbiology and immunology. Dr. Feinberg is leading the Vaccine Center’s program in clinical trials development for HIV vaccines.

Harriet Robinson, Ph.D., who joined the Vaccine Center in 1997 and serves as the Yerkes chief of microbiology and immunology, is a pioneer in vaccine development for retroviruses. Dr. Robinson became internationally known as the first person to demonstrate that purified DNA can be used as a safe, effective vaccine. Recently she created a DNA vaccine that protects monkeys against a formidable challenge HIV virus. Achieving protection with this vaccine, made with harmless components from SHIV -- a blend of parts from HIV and SIV (simian or monkey immunodeficiency virus) -- marks a significant and promising step toward the development of an effective AIDS vaccine.

In addition to HIV vaccine research, the new Vaccine Center includes a major research program on malaria vaccines, led by Mary Galinski, Ph.D. Dr. Galinski is conducting groundbreaking genetic research in collaboration with investigators at the Centers for Disease Control and Prevention. She also is a leader in global malaria initiatives focused on collaborative research, funding sources, government involvement and prevention efforts.

The Vaccine Center also houses the world’s only facility for making tetramers, a powerful new technology developed by Emory immunologist John Altman, Ph.D., that is referred to as the "gold standard" for enabling scientists to demonstrate how the immune system is responding to specific viruses and to vaccines. Emory’s Tetramer Core Facility, funded by the NIH, not only will serve the needs of Emory investigators, but also will prepare custom tetramer testing for investigators throughout the country.

A new DNA Microarray Facility, a collaborative facility located in the Vaccine Center and funded by the Georgia Research Alliance, includes four Georgia research universities. The Microarray Facility will allow Emory genetics experts to use sequencing information recently made available through the Human Genome Project to assess changes in the expression of thousands of genes simultaneously. The new technology is expected to dramatically enhance the ability of scientists and clinicians to conduct basic genetic research, provide more accurate disease diagnosis and prognosis, and develop new drugs and vaccines that target the genetic basis of disease.

The Georgia Research Alliance, a non-profit, public-private partnership of research universities, business and state government, has provided generous support for the Vaccine Center in a belief that Georgia is "well-poised to lead the next era of vaccine development," according to GRA director William Todd. The center also is funded by the National Institutes of Health and the federal Office of AIDS Research.

Rafi Ahmed, Ph.D.
Understanding the intricacies of long-term immune memory is a key to vaccine development. Rafi Ahmed, Director of the Emory Vaccine Center and the Georgia Research Alliance Eminent Scholar, is an internationally recognized expert on viral persistence and the immune response to viruses. Dr. Ahmed and his colleagues have made important discoveries about the differences between the two types of immune memory—humoral and cellular. Dr. Ahmed has shown that plasma cells, the cells that produce antibodies to prevent viral infection (humoral immunity), live for much longer than previously believed, perhaps even for the entire life of an organism. His laboratory is now trying to uncover the mechanisms that result in the generation of long-lived plasma cells. Dr. Ahmed and his colleagues also have discovered that CD8 T cells, the cells that are activated by viral antigens to kill cells that are already infected (cellular immunity), respond at their peak for only a few weeks, after which a small percentage become memory cells capable of mounting a stronger and more rapid immune response if reintroduced to the original virus. Studies to elucidate the molecular basis of T cell memory are being pursued in the laboratory. The long-term goal of Dr. Ahmed’s research is to understand the mechanisms of immunological memory and to use this information to develop new vaccines for the prevention and treatment of disease.

John Altman, Ph.D.
Most scientists agree that an AIDS vaccine will be effective only if it generates both humoral and cellular immune responses. John Altman recently developed a new technology called the tetramer assay that is able to demonstrate how effectively the immune system is responding to viruses. The tetramer test has been called "the new gold standard" for measuring specific immune responses to viruses. In addition, the new technology for the first time provides a detailed picture of the normal and abnormal cellular immune responses to infection. Dr. Altman and his colleagues will now be able to use the new test to demonstrate how effective a particular vaccine is in raising a cellular response. With funding from the NIH, Dr. Altman has established a national tetramer core facility at Emory that prepares custom tetramer testing for investigators around the country.

Richard Compans, Ph.D.
Although three-fourths of all HIV transmissions are sexual and not blood borne, most HIV vaccines thus far offer little protection when the initial viral contact is made at the genital-mucosal membrane. Richard Compans and his colleagues are working to develop a two-part vaccine for HIV, with one part injected and the other taken orally to stimulate the mucosal immune system. The combination has shown remarkable success in protecting rhesus macaques against vaginal infection by the simian immunodeficiency virus (SIV). Dr. Compans has been developing a DNA model of the macaque vaccine, as well as a method of transporting the oral part of the vaccine safely through the digestive system. His team is now trying to determine exactly how the vaccine prevents infection, whether the immune response will work against different strains of the virus and how long the immune response will last.

Mark Feinberg, M.D., Ph.D.
Mark Feinberg is an associate professor of medicine and microbiology and immunology who also serves as associate director of the Emory/Atlanta Center for AIDS Research (CFAR). Dr. Feinberg has been a national leader in HIV research since the earliest days of the epidemic. Prior to joining the Emory faculty in 1998, he served as medical officer for the Office of AIDS Research at the National Institutes of Health. At Emory, Dr. Feinberg and his colleagues are leading a step-by-step program in vaccine development that will take HIV vaccines from the most basic laboratory research to clinical trials in humans. Dr. Feinberg and colleagues are developing new vaccine vectors to immunize against HIV infection, and studying ways to augment the magnitude and longevity of immune responses induced by candidate HIV vaccines. Within the next few months, Emory scientists will begin human trials of novel HIV vaccines developed by pharmaceutical and biotech companies. Within two years, they hope to begin testing Emory-developed HIV vaccines.

Mary Galinski, Ph.D.
Malaria is a complex disease of worldwide epidemic proportions in about 100 countries, with up to
500 million new clinical cases – most of them children – estimated each year. Although some treatments are available for malaria, drug resistance is widespread, and large segments of the world’s population do not have access to the most effective remedies. Further, there is as yet no vaccine for malaria. Malaria parasites undergo major changes as they reproduce in Anopheline mosquitoes and then infect the liver and blood of vertebrate hosts. Mary Galinski and her team are focused on understanding molecular genetic and immunobiological aspects of requisite parasite-host adaptations for the most prevalent types of human malaria, with concurrent use of simian (monkey) malaria model systems. Their research involves basic as well as population-based studies
of people from several regions of the world. Dr. Galinski also is conducting simian vaccine trials that are pathfinders for eventual human malaria vaccine trials. In addition to her research program, Dr. Galinski is an international leader in the effort to raise public and governmental awareness of malaria’s widespread health threat. She is founder of the Malaria Foundation International, a nonprofit organization dedicated to promoting research, prevention and control of the disease, and is an active participant through foundation activities in three new major global programs to combat malaria: the Multilateral Initiative on Malaria, Roll Back Malaria and the Malaria Vaccine Initiative.

Scott Hemby, Ph.D.
Pharmacologist Scott Hemby is director of the new DNA Microarray Facility, a collaborative facility funded by the Georgia Research Alliance that includes four other Georgia research universities. The Emory Core Laboratory contains DNA microarray ("chip") technology that Emory geneticists will use to examine changes in the DNA of thousands of genes simul-taneously. Using the DNA chip technology, scientists will array complementary DNA (cDNA) or oligonucleotides, representative of specific genes, on small chips. The chips will then be probed with RNA or DNA. In order to compare diseased tissue to normal tissue, for example, scientists will probe DNA chips with fluorescently labeled RNA extracted from tissue or blood. RNA that matches genetic sequences arrayed on the chip will fluoresce (glow) when read by a special laser scanner. Examining changes in the expression of multiple genes should reveal a "molecular fingerprint" of the disease, specific genetic mutations, genetic changes during dif-ferent stages of the disease process, and genetic function, as well as response to drugs or vaccines. With current technology, the sequences from as many as 10,000 genes can be placed on one small chip. In the near future, scientists expect to be able to array 30,000 sequences on a single chip.

Abdul Jabbar, Ph.D.
In order for immune lymphocytes to attack viruses, the viruses must present antigens that the immune system recognizes as foreign invaders. One reason the HIV-1 virus is elusive to the immune system is its ability to attack the very cells (CD4+ T lymphocytes) that provide an effective defense against invading pathogens. HIV envelope-based vaccines (gp160 and gp120) do not induce long-lasting immunity due to the low level of immunogenicity, or weak antigen presentation they induce, as well as the transient nature of this immunogenicity. Abdul Jabbar is focusing on HIV proteins, such as gp160 and Vpu, that target CD4 for intracellular degradation. In particular, the HIV-1 Vpu protein induces the degradation of glycoproteins with CD4 sequences. Dr. Jabbar plans to use this property of the protein to induce relatively robust immune responses in animals. He also is modifying other HIV proteins, including gp160 and gp120, with the hope of enhancing and prolonging immunogenicity. He plans to introduce the modified proteins as DNA vaccines, first in mice, then in monkeys. The enormous genetic diversity of varieties of the HIV virus also makes vaccine design difficult. Although there are more than 10 distinct genetic groups of the HIV virus worldwide, most infections in North America result from subtype B. HIV-1 subtype C, on the other hand, accounts for more than half of HIV cases globally. Dr. Jabbar believes his studies may lead to improved strategies for universal vaccine design.

Joshi Jacob, Ph.D.
Joshi Jacob and his colleagues recently discovered a new method of permanently marking T cells that will allow immunologists to distinguish which ones become memory cells —the 5 to 10% of T lymphocytes that survive and retain the ability to mount a strong immune response when confronted with the original virus. Research into the mechanisms of immune memory has been hampered because scientists have been unable to identify these memory lymphocytes from other T cells. Using the new technique, Dr. Jacob irreversibly tagged T lymphocytes in mice with a cell surface protein, called a "reporter gene," which he permanently activated by recombining fragments of DNA. Since the key to designing good vaccines is understanding how immune memory works, the ability to map and follow memory cells should yield important clues about how immune memory is generated and maintained. Dr. Jacob believes the discovery will have far-reaching implications for vaccine development, transplantation, and treatment of auto-immune diseases.

Frank Novembre, Ph.D.
In their quest to develop an effective HIV vaccine, Frank Novembre and his colleagues modified a highly pathogenic isolate of simian immunodeficiency virus (SIV) so that it could not cause disease, but still induced a protective immune response. This modified SIV contained a deletion in the nef gene. Scientists have determined that the nef gene encodes a protein that is involved in shielding the virus from immune responses by modifying protein expression on the surface of infected cells. Dr. Novembre believes that these viruses, while controversial in their possible use as vaccine candidates, will be extremely useful in helping reveal specific mechanisms of the immune response that protect animals against infection. A future goal is to include the Nef protein of this virus (expressed via DNA immunization) as an adjunct to the live attenuated virus, to examine possible contributions to protection.

Harriet Robinson, Ph.D.
Harriet Robinson is Chief of Microbiology and Immunology at Yerkes Research Center. A DNA vaccine pioneer, she was one of the first scientists to demonstrate that purified DNA could be used as a safe and effective vaccine. Dr. Robinson was lead author of the comprehensive American Society of Microbiology guide to DNA vaccines. DNA vaccines are able to raise both humoral and cellular immune responses. And, since they are constructed using only selected components of a pathogen, they are safer than many conventional vaccines. Dr. Robinson recently created a DNA vaccine that, when paired with a recombinant pox virus boost, was remarkably effective in protecting macaque monkeys against a formidable challenge with a virulent SHIV virus — a combination of simian immunodeficiency virus and HIV. In ongoing studies, Dr. Robinson’s team is refining the DNA vaccine protocol with plans to initiate phase I studies in humans.
Jeff Safrit, Ph.D.

Scientists have discovered that if a patient’s early cellular response to HIV infection is weak, that patient’s longterm prognosis will be poor. A strong T cell response late in the course of infection can be equally harmful, however, because in killing the virus, the immune system can eliminate the few CD 4 lymphocytes that remain to fight opportunistic infections. Dr. Safrit is studying specific components of the cellular immune response to HIV infection during different stages of the disease. He and Dr. Altman are developing an assay that will allow the tetramer assay to measure function as well as intensity of the T cell response. In addition, Dr. Safrit is collaborating with other Vaccine Center scientists to examine the immune responses to a number of candidate AIDS vaccines.

Silvija Staprans, Ph.D.

The immune response to viruses and, in turn, the viral response to the immune system, is governed by a variety of complex factors. The HIV virus, in particular, is capable of eluding the immune response and of persisting even in the face of strong antiviral therapy. Silvija Staprans and her colleagues are focusing their research on the link between immune activation and virus replication. She is especially interested in the early host lymphocyte and virus interactions that determine whether the initial HIV infection results in a protective host response against the virus or an ineffective or harmful response to the virus. The study of the dynamics of virus-immune system responses requires precise measures of virus replication. Dr. Staprans is developing refined testing methods for viral response. In collaboration with other investigators, she also is studying a population of monkeys called mangabeys that are naturally infected with simian immunodeficiency virus (SIV) but do not develop AIDS. By comparing these mangabeys to macaque monkeys that develop AIDS after infection with SIV, she hopes to learn more about virus-immune system interactions.


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