Novel tuberculosis vaccines on the horizon.
ABSTRACT Eleven new tuberculosis (TB) vaccines are in various phases of clinical trials. These include subunit vaccines to improve the current vaccine BCG, and recombinant BCG to substitute for BCG, both given pre-exposure to prevent active disease. A plethora of potential candidates have reached various stages of the pre-clinical development pipeline, some ready to enter Phase I clinical trial soon. A boost vaccine to top up the immunity of existing BCG is on the horizon and will have to suffice until a better candidate to replace BCG is ready. The live mutants of Mycobacterium tuberculosis show great promise, but face a myriad of regulatory challenges.
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ABSTRACT: Tuberculosis is both highly prevalent across the world and eludes our attempts to control it. The current BCG vaccine has unreliable protection against adult pulmonary tuberculosis. As a result, tuberculosis vaccine development has been an ongoing area of research for several decades. Only recently have research efforts resulted in the development of several vaccine candidates that are further along in clinical trials. The majority of the barriers surrounding tuberculosis vaccine development are related to the lack of defined biomarkers for tuberculosis protective immunity and the lack of understanding of the complex interactions between the host and pathogen in the human immune system. As a result, testing various antigens discovered through molecular biology techniques have been only with surrogates of protection and do not accurately predict protective immunity. This review will address new discoveries in latency antigens and new next generation candidate vaccines that promise the possibility of sterile eradication. Also discussed are the potentially important roles of systems biology and vaccinomics in shortening development of an efficacious tuberculosis vaccine through utilization of high throughput technology, computer modeling, and integrative approaches.Respirology 01/2013; · 2.78 Impact Factor
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ABSTRACT: Severe combined immunodeficiency (SCID) is a syndrome characterized by profound T-cell deficiency. BCG vaccine is contraindicated in patients with SCID. Because most countries encourage BCG vaccination at birth, a high percentage of patients with SCID are vaccinated before their immune defect is detected. We sought to describe the complications and risks associated with BCG vaccination in patients with SCID. An extensive standardized questionnaire evaluating complications, therapeutics, and outcomes regarding BCG vaccination in patients given a diagnosis of SCID was widely distributed. Summary statistics and association analysis was performed. Data on 349 BCG-vaccinated patients with SCID from 28 centers in 17 countries were analyzed. Fifty-one percent of the patients had BCG-associated complications, 34% disseminated and 17% localized (a 33,000- and 400-fold increase, respectively, over the general population). Patients receiving early vaccination (≤1 month) showed an increased prevalence of complications (P = .006) and death caused by BCG-associated complications (P < .0001). The odds of experiencing complications among patients with T-cell numbers of 250/μL or less at diagnosis was 2.1 times higher (95% CI, 1.4-3.4 times higher; P = .001) than among those with T-cell numbers of greater than 250/μL. BCG-associated complications were reported in 2 of 78 patients who received antimycobacterial therapy while asymptomatic, and no deaths caused by BCG-associated complications occurred in this group. In contrast, 46 BCG-associated deaths were reported among 160 patients treated with antimycobacterial therapy for a symptomatic BCG infection (P < .0001). BCG vaccine has a very high rate of complications in patients with SCID, which increase morbidity and mortality rates. Until safer and more efficient antituberculosis vaccines become available, delay in BCG vaccination should be considered to protect highly vulnerable populations from preventable complications.The Journal of allergy and clinical immunology 04/2014; 133(4):1134-41. · 12.05 Impact Factor
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ABSTRACT: The care of patients with respiratory diseases has improved vastly in the past 50 years. In spite of that, there are still massive challenges that have not been resolved. Although the incidence of tuberculosis has decreased in the developed world, it is still a significant public health problem in the rest of the world. There are still over 2 million deaths annually from tuberculosis, with most of these occurring in the developing world. Even with the development of new pharmaceuticals to treat tuberculosis, there is no indication that the disease will be eradicated. Respiratory syncytial virus, severe acute respiratory syndrome, and pertussis are other respiratory infectious diseases with special problems of their own, from vaccine development to vaccine coverage. Asthma, one of the most common chronic diseases in children, still accounts for significant mortality and morbidity, as well as high health care costs worldwide. Even in developed countries such as the USA, there are over 4,000 deaths per year. Severe asthma presents a special problem, but the question is whether there can be one treatment pathway for all patients with severe asthma. Severe asthma is a heterogeneous disease with many phenotypes and endotypes. The gene for cystic fibrosis was discovered over 24 years ago. The promise of gene therapy as a cure for the disease has fizzled out, and while new antimicrobials and other pharmaceuticals promise improved longevity and better quality of life, the average life span of a patient with cystic fibrosis is still at about 35 years. What are the prospects for gene therapy in the twenty-first century? Autoimmune diseases of the lung pose a different set of challenges, including the development of biomarkers to diagnose and monitor the disease and biological modulators to treat the disease.Clinical Reviews in Allergy & Immunology 11/2013; · 5.59 Impact Factor