Progress in tuberculosis vaccine development and host-directed therapies--a state of the art review.
Tuberculosis continues to kill 1·4 million people annually. During the past 5 years, an alarming increase in the number of patients with multidrug-resistant tuberculosis and extensively drug-resistant tuberculosis has been noted, particularly in eastern Europe, Asia, and southern Africa. Treatment outcomes with available treatment regimens for drug-resistant tuberculosis are poor. Although substantial progress in drug development for tuberculosis has been made, scientific progress towards development of interventions for prevention and improvement of drug treatment outcomes have lagged behind. Innovative interventions are therefore needed to combat the growing pandemic of multidrug-resistant and extensively drug-resistant tuberculosis. Novel adjunct treatments are needed to accomplish improved cure rates for multidrug-resistant and extensively drug-resistant tuberculosis. A novel, safe, widely applicable, and more effective vaccine against tuberculosis is also desperately sought to achieve disease control. The quest to develop a universally protective vaccine for tuberculosis continues. So far, research and development of tuberculosis vaccines has resulted in almost 20 candidates at different stages of the clinical trial pipeline. Host-directed therapies are now being developed to refocus the anti-Mycobacterium tuberculosis-directed immune responses towards the host; a strategy that could be especially beneficial for patients with multidrug-resistant tuberculosis or extensively drug-resistant tuberculosis. As we are running short of canonical tuberculosis drugs, more attention should be given to host-directed preventive and therapeutic intervention measures.
Department of Immunology, Max Planck Institute for Infection Biology, Berlin, Germany.
Stefan H E
SH
Kaufmann
Division of Clinical Infectious Diseases, Medical Clinic, Research Center Borstel, German Center for Infection Research (DZIF), Borstel, Germany.
Christoph
C
Lange
Center for Allogeneic Stem Cell Transplantation (CAST), Therapeutic Immunology (TIM), Department of Laboratory Medicine, Karolinska Institutet, Stockholm, Sweden.
Martin
M
Rao
Department of Microbiology and Cell Biology, Indian Institute of Science, Bangalore, Karnataka, India.
Kithiganahalli N
KN
Balaji
University of Pittsburgh Cancer Institute, Pittsburgh, PA, USA; University of Pittsburgh Schools of the Health Sciences, Hillman Cancer Center, Pittsburgh, PA, USA.
Michael
M
Lotze
Henry M Jackson Foundation-Division of AIDS, TB Clinical Research Branch, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD, USA.
Marco
M
Schito
Centre for Clinical Microbiology, Division of Infection and Immunity, University College London, London, UK; UCL Hospitals NHS Foundation Trust, London, UK.
Alimuddin I
AI
Zumla
Center for Allogeneic Stem Cell Transplantation (CAST), Therapeutic Immunology (TIM), Department of Laboratory Medicine, Karolinska Institutet, Stockholm, Sweden. Electronic address: Markus.Maeurer@ki.se.
Markus
M
Maeurer
D000995:Antitubercular Agents; D035843:Biomedical Research; D006801:Humans; D009169:Mycobacterium tuberculosis / Q000187:drug effects / Q000276:immunology; D014376:Tuberculosis / Q000188:drug therapy* / Q000276:immunology / Q000517:prevention & control; D032581:Tuberculosis Vaccines
D000995:Antitubercular Agents; D032581:Tuberculosis Vaccines