Select a year 2001 2002 2003    Select a researcher Alan G. Barbour, M.D. William Bishai, M.D., Ph.D. Martin J. Blaser, M.D. John C. Boothroyd, Ph.D. Jon Clardy, Ph.D. Peter Cresswell, Ph.D. Roy Curtiss, III, Ph.D. Ronald W. Davis, Ph.D. Jack E. Dixon, Ph.D. Stanley Falkow, Ph.D. Gerald R. Fink, Ph.D. Richard A. Flavell, Ph.D. Lee Gehrke, Ph.D. Laurie H. Glimcher, M.D. Jeffrey I Gordon, M.D. Daniel L. Hartl, Ph.D. William R. Jacobs, Jr., Ph.D. Keith A. Joiner, M.D., co-PI Karla Kirkegaard, Ph.D. Roberto G. Kolter, Ph.D. W. Ian Lipkin, M.D. Richard M. Locksley, M.D. Carl Nathan, M.D. Peter Palese, Ph.D. Pradipsinh K. Rathod, Ph.D. David A. Relman, M.D. Charles M. Rice, Ph.D. Alexander Rich, M.D. Lee W. Riley, M.D. David S. Roos, Ph.D. Abigail A. Salyers, Ph.D. Gary K. Schoolnik, M.D. Iwona Stroynowski, Ph.D. Ronald P. Taylor, Ph.D. Elisabetta Ullu, Ph.D. John Waitumbi, D.V.M., Ph.D Select a project A Gnotobiotic Zebrafish Model for Analyzing Symbiotic Host...Antiviral Effects of Interferon-Inducible Cytosolic ProteinsArming the Immune System against Pathogens with Selective ...Bacterial Pathogen Families that Function in Both the Anim...Cellular Genes and Viruses: Who Wins The War?Conditional Targeted Deletions in Plasmodium falciparum...Designing and Mining Pathogen Genome Databases: The Apicop...Development of Genetic Systems for Genetically Intractable...Development of New Genetic Tools to Identify Nutrient Upta...Ecological Influences on Pathogen Genome EvolutionEvolution of Virulence in Eukaryotic PathogensExploiting an Evolutionary Omission in Pathogenic RNA Viru...Exploring Novel Pathways of Immune Defenses Against Orally...Genomic Approach to Improved Immunogenicity of M. tuber...Genomic tools to characterize hypermutating Plasmodium fal...Investigation of Mechanisms Leading to Anemia at Low Paras...Molecular definition of the bacterial population of human ...Mycobacterium Tuberculosis Latency and Reactivation Tuberc...New Antibiotics from Environmental DNAOptimizing Immunity to Complex Pathogens In VivoPandora's Box ProjectProviding an Economic Benefit to Using a Vaccine to Enhanc...Resistance Gene Flow in the Human Colonic MicrofloraRole of Nucleotide Binding Domain-Leucine Rich Repeat Prot...Sexually Transmitted Disease Agents in the “Healthy” Human...Systematic Analysis of Positive-strand RNA Viral Transmiss...The Human Intestinal Microbiome: Community Analysis, Host ...The Molecular Ecology of Vibrio cholerae in the Gangetic D...The Natural History of Typhoid Infection in VietnamThe Role of Quorum Sensing in Fungal DiseaseTowards Broad-spectrum Antivirals: Functional Screens for ...Transmission Blocking Vaccines for TuberculosisTransmission-blocking Vaccines Against Arthropod VectorsViral Pathogenic Mechanisms Involving Z-DNA Binding Proteins Select an institution Albert Einstein College of Medicine of Yeshiva University Columbia University Harvard Medical School Harvard School of Public Health Harvard University Johns Hopkins School of Public Health Massachusetts Institute of Technology Mount Sinai School of Medicine New York University School of Medicine Rockefeller University Stanford University School of Medicine Stanford University School of Medicine, VA Palo Alto Health Care System University of California - Berkeley University of California - Irvine University of California - San Diego University of California - San Francisco University of Illinois - Urbana-Champaign University of Pennsylvania University of Texas Southwest Medical Center University of Virginia University of Washington Washington University Washington University School of Medicine Weill Medical College of Cornell University Whitehead Institute for Biomedical Research Yale University School of Medicine

Carl Nathan, M.D. Weill Medical College of Cornell University

Clearly we need a highly effective vaccine. Because people are the only known hosts for Mtb, it might even be possible to eliminate tuberculosis entirely by a combination of high-efficiency vaccination and antibiotic regimens that work faster and more broadly than those presently in hand. However, putting aside the technical, fiscal and social challenges, there are enormous biological challenges in trying to improve on the marginally effective Mtb vaccine currently in use or the experimental vaccines now in development. First, infection by Mtb, or even full-blown tuberculosis that is treated and cured, do not protect a person against getting infected with Mtb again. Second, antibodies offer no protection in experimental animals; only cell-mediated immunity appears to protect, and much less is known about how to induce strong cell-mediated immunity. Third, no adjuvants (vaccine-augmenting agents) are available for clinical use that induce cell-mediated immunity as well as Mtb, and yet, as noted, Mtb does not induce clinically effective cell-mediated immunity against itself. Fourth, among those most in need of a vaccine are HIV positive people whose capacity for cell-mediated immunity is particularly weak. In sum, Mtb itself should be the best Mtb vaccine because it offers all its antigens and is a strong adjuvant, and yet Mtb is both a poor vaccine and a dangerous one. Thus it is hardly surprising that protection is limited following vaccination with BCG (the current standard), a mycobacterium that is safer than Mtb because it has lost many genes; or with Mtb that has been crippled to make it safer than BCG by deleting genes needed for growth in people; or by small numbers of individual Mtb antigens administered as DNA preparations, as pure proteins, or as proteins expressed artificially in other types of bacteria that can be administered safely.

The present project is based on the view that Mtb is an extremely complex collection of antigens. Some Mtb antigens induce protective immune responses. But other Mtb antigens interfere with induction of protective immune responses, or even induce counter-protective responses. The goal of this project is to query each of the 4000 genes of Mtb and systematically identify those genes whose products elicit counterproductive host responses. In the future, such genes can be deleted in Mtb, along with genes identified by others as necessary for growth in people. The resulting variants of Mtb may be both safer and more effective as a vaccine than Mtb itself.

Contact Dr. Nathan.