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Medical Specialties / Infectious Diseases / Tuberculosis


The Contribution of Non-human Primate Models to the Development of Human Vaccines

Abstract: The non-human primates (NHPs) model in biomedical research has contributed to the study of human infectious, autoimmune, oncogenic, and neurological diseases. This review focuses on the importance of NHP models in vaccine development for tuberculosis, pertussis, Dengue, group A streptococcus (Streptococcus pyogenes) infection, HIV infection, and certain diseases in the elderly (influenza, for example). From understanding disease pathogenesis and mechanisms of protection, to assessing vaccine safety and efficacy, we discuss selected cases where the importance of the use of NHP models is highlighted. ... Read more

Point-of-Care Diagnostics for HIV and Tuberculosis: Landscape, Pipeline, and Unmet Needs

Abstract: Early diagnosis and rapid initiation of treatment remains a key strategy to control both HIV and tuberculosis (TB). However, HIV and TB control programs have had completely contrasting successes, especially with the development and deployment of point-of-care (POC) diagnostics. Clinicians, researchers, and public health staff who work at the frontlines of HIV care and control have had access to an outstanding array of POC diagnostics at their disposal, including those used for screening, initial diagnosis, staging, treatment monitoring, and early infant diagnosis. The field has also advanced to consider over-the-counter, self-testing options for HIV and the use of multiplexed platforms that allow for simultaneous detection of infections associated with HIV. In sharp contrast to HIV, suboptimal and delayed diagnosis of TB has perpetuated the epidemic in many high-burden countries. Although the TB diagnostics pipeline is substantially better today than it was even five years ago, absence of a simple POC test continues to be a gaping hole in the pipeline. In this review, we compare the POC diagnostics landscape and pipelines for these two important infectious diseases, and highlight gaps and unmet needs. ... Read more

Vaccine Adjuvant Properties of Probiotic Bacteria

Abstract: Vaccine-preventable diseases are still responsible for the deaths of more than 1 million children under the age of 5 years annually, mostly in developing countries. A substantial number of these deaths are due to pneumococcal bacteria and infections with rotavirus. Important issues faced by the WHO, governments, vaccine manufacturers, and international organizations such as UNICEF and the Global Alliance for Vaccines and Immunization (GAVI) are the cost-effective introduction of these life-saving vaccines in resource-poor countries where there is a considerable disease burden, and achieving high rates of completion of vaccination schedules remains elusive. Problems with vaccine coverage and vaccine delivery in these regions are significant, as in some cases large proportions of the target population do not receive adequate vaccination. Consequently, there is a need to develop more effective vaccination strategies that can provide adequate protection with reduced schedules. To date, emphasis has been placed on identifying novel vaccine antigens and adjuvants that induce stronger protective immune responses, as well as developing mucosally-administered vaccines. These approaches would have enormous benefits in allowing safe administration of vaccines in remote areas and may overcome the necessity for multiple doses. In this regard, the use of probiotic bacteria as novel mucosal adjuvants to enhance existing vaccine specific-immune responses offers an exciting new approach. In this review, we discuss the evidence for the role of probiotics in enhancing vaccine responses and provide justification for further investigation into their clinical effects and mechanisms of action. ... Read more

Promotion of a Down-modulated Lung Immune State May Be a Strategy by M. tuberculosis to Foster Active Disease and Persistence

Abstract: One-third of humans carry Mycobacterium tuberculosis, the etiological agent of tuberculosis (TB) where microbe/host immune response interactions result in persistence or active TB. However, immune mediators associated with human TB remain poorly defined. Through a series of comparative studies of lung immune response of TB cases at the time of diagnosis and patients with other infectious lung diseases and volunteers, we found that TB cases expressed significantly higher levels of mediators that counteract Th1-type and innate immunity critical for containment of M. tuberculosis. Despite the concomitant heightened levels of Th1-type mediators, they are likely rendered ineffectual by high levels of intracellular (e.g., SOCS) and extracellular (e.g., IL-10) immune suppressors. These modulators are a direct response to M. tuberculosis as many suppressive factors declined to the levels of controls by 30 days of anti-TB treatment while most Th1-type and innate immune mediators rose above the pre-treatment levels. Parallel laboratory studies and monitored lung alveolar macrophage effector, nitric oxide synthase-2 (being shown critical for killing M. tuberculosis), support that M. tuberculosis actively promotes down-modulatory mediators to counteract Th1-type/innate immunity as an immunopathological strategy. Our studies highlight the potential application of immune mediators as surrogate markers for TB diagnosis or treatment response. ... Read more

DNA Vaccines: Recent Technological and Clinical Advances

Abstract: DNA vaccines generate both T cell and B cell (or antibody) mediated immunities. Methods such as prime-boost regimens and the use of adjuvants in combination with the DNA vaccine have enhanced the therapeutic effectiveness of DNA vaccines in the treatment of cancer, infectious diseases, autoimmune diseases, asthma, and other conditions. ... Read more

Battle for Survival: Interplay Between Pathogenic Mycobacteria and the Host Immune System

Abstract: Mycobacteria tuberculosis infects about one third of the world population in their life times and causes millions of deaths each year. M. tuberculosis has a unique capability to circumvent the bactericidal activities of macrophages - the frontline defenders of the host immunity. New understanding of this mechanism has positioned scientists to develop therapies that allow host immune system to gain an upper hand. ... Read more

Editor's Note -- October 2005

Western medicine treats a patient’s disease. Traditional Chinese medicine, one of the longest practiced and used by the most number of people, treats a diseased patient (see Dr. Jiang’s article on page 455). It makes the most sense to treat both the patient’s disease and the diseased patient.

Tuberculosis is a disease that illustrates the importance of both aspects in curing it. Mycobacterium tuberculosis invades and dwells in a compromised body with a weakened immune system. Since the bacteria live within cells, it takes persistent use of anti-mycobacterial drugs for an extended period of time to contain the bacteria. To completely ... Read more

Learning From BCG: Designing a Better Tuberculosis Vaccine

Abstract: Widely used TB vaccine BCG protects children from TB much more effectively than adults. The reason: prior to BCG vaccination, many adults were exposed to Mycobacterium tuberculosis or atypical mycobacterium species such as M. avium and subsequently developed variable levels of cross-immunity against the BCG. For protecting the adult population, a genetically modified BCG vaccine should be explored. ... Read more

Quotes on Biomedical Science and Biotechnology/Pharmaceutical Industry

“Science requires greater modesty. Our experience with AIDS underscores the importance of basic research, which gave us the technical and conceptual tools to find the cause in less than three years after the disease was first described… It has also become clear that finding the cause of an infectious disease is the alpha but not the omega of its eradication.”

Robert C. Gallo, M.D., and Luc Montagnier, M.D., Director of Institute of Human Virology, University of Maryland, Baltimore (R.C.G); World Foundation AIDS Research and Prevention, Paris (L.M.). In “The Discovery of HIV as the cause of AIDS.” N Engl J Med ... Read more

Antisense therapeutics show promise in cancer treatment

Antisense technology is based on a simple and beautiful concept: a short stretch of DNA, whose sequence is complementary to a specific mRNA of interest, binds to the target and induces its degradation or blocks its expression. Since the first application of antisense DNA on Rous sarcoma virus expression in 1978, numerous DNA oligos have undergone clinical trials. In over two decades of developing this technology, scientists have accumulated a lot of valuable information.

In order to avoid degradation, antisense DNA oligos have to be modified to increase ... Read more

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