Catalogue Search | MBRL
Are you sure you want to remove the book from the shelf?
{{itemTitle}}
248
result(s) for
"Tuberculosis Vaccines history."
Sort by:
Envisioning future strategies for vaccination against tuberculosis
Stefan Kaufmann looks to the future of vaccination against tuberculosis. By drawing on past and present vaccination approaches, he proposes that the most successful strategy for preventing tuberculosis in the future will combine different vaccine candidates and use a prime–boost approach.
The design of tuberculosis vaccines has entered a new era. Although several new vaccine candidates will pass Phase I clinical trials within the next year, I believe that the most effective vaccination strategy will be to combine different vaccine candidates and to use a prime–boost approach. This strategy, however, would require several years of iterative vaccine trials, unless the process is expedited by the identification of reliable biomarkers for assessing vaccine efficacy. In this Essay, I briefly summarize past and present attempts to develop a vaccine against tuberculosis, and I describe, using imagined scenarios, the tuberculosis vaccination schemes that might become available from a large repertoire of candidate schemes in the near and distant future.
Journal Article
Immunoprophylaxis of Tuberculosis: An Update of Emerging Trends
Developing effective prophylactics to combat tuberculosis is currently in an exploratory stage. The HIV pandemic and emergence of multi- and extensively drug-resistant strains of Mycobacterium tuberculosis indicate that the current preventive measures against this ever-evolving pathogen are inadequate. The currently available vaccine BCG in its present form affords variable protection which usually wanes with aging. Various reasons have been cited to explain the discrepancies in the efficacy of BCG, including generic differences in the different BCG vaccine strains used in immunization program throughout the world. The low efficacy of BCG vaccine has promoted the search for novel vaccines for tuberculosis. The search strategies aim at completely replacing the existing vaccine and/or augmenting/improving the current BCG vaccine. Among new vaccine candidates are live attenuated M. tuberculosis vaccines, recombinant BCG, DNA vaccines, subunit vaccine, and fusion protein-based vaccines. More than 200 new vaccine candidates have been developed as a result of research work over the past few years. To date, at least eight vaccine candidates are undergoing clinical evaluation, with a few of them successfully qualifying in the first phase of clinical testing. These recent advances present an optimistic insight whereby a new tuberculosis vaccine might be expected to be available for public use in the next few years.
Journal Article
Tuberculosis vaccines: the past, present and future
Tuberculosis still remains a leading infectious cause of death worldwide, although the BCG vaccine has been used for 80 years. There is an urgent need to develop improved BCG or new tuberculosis vaccines. This apparently represents a daunting task, since it will take a long time before a vaccine can be declared to be better than the current BCG vaccine, both in experimental and human studies. The current review takes a brief historic look at the use of current BCG vaccine and provides an overview on what are considered to be the key immunologic criteria that have to be met by a new generation of tuberculosis vaccines. It also provides the most up-to-date information on the latest developments in tuberculosis vaccine research, with a focus on mycobacterial organism-based and Mycobacterium tuberculosis antigen-based vaccines. Consideration is also given to the mucosal route of immunization and 'prime and boost' regimens. This review also presents several important tables, highlighting critical components of antituberculosis immunity, the most commonly tested immune adjuvants, the types of novel tuberculosis antigen-based vaccines and the outcome of different heterologous 'prime and boost' vaccination regimens.
Journal Article
Final Analysis of a Trial of M72/AS01E Vaccine to Prevent Tuberculosis
Mycobacterium tuberculosis
remains a major global health threat. In this report, the M72/AS01
E
vaccine provided approximately 50% protection against progression to active tuberculosis disease in adults.
Journal Article
100 years of Mycobacterium bovis bacille Calmette-Guérin
Mycobacterium bovis bacille Calmette-Guérin (BCG), an experimental vaccine designed to protect cattle from bovine tuberculosis, was administered for the first time to a newborn baby in Paris in 1921. Over the past century, BCG has saved tens of millions of lives and has been given to more humans than any other vaccine. It remains the sole tuberculosis vaccine licensed for use in humans. BCG provides long-lasting strong protection against miliary and meningeal tuberculosis in children, but it is less effective for the prevention of pulmonary tuberculosis, especially in adults. Evidence mainly from the past two decades suggests that BCG has non-specific benefits against non-tuberculous infections in newborn babies and in older adults, and offers immunotherapeutic benefit in certain malignancies such as non-muscle invasive bladder cancer. However, as a live attenuated vaccine, BCG can cause localised or disseminated infections in immunocompromised hosts, which can also occur following intravesical installation of BCG for the treatment of bladder cancer. The legacy of BCG includes fundamental discoveries about tuberculosis-specific and non-specific immunity and the demonstration that tuberculosis is a vaccine-preventable disease, providing a foundation for new vaccines to hasten tuberculosis elimination.
Journal Article
Safety and immunogenicity of the novel H4:IC31 tuberculosis vaccine candidate in BCG-vaccinated adults: Two phase I dose escalation trials
•H4:IC31 vaccination was well tolerated with an acceptable safety profile.•H4:IC31 vaccination elicited persistent antigen-specific CD4+ T cell responses.•H4:IC31 triggered T cell expansion, IFNγ production and multifunctional Th1 cells.•Optimal antigen-adjuvant doses were 5, 15, or 50 μg of H4 plus 500 nmol of IC31.
Novel vaccine strategies are required to provide protective immunity in tuberculosis (TB) and prevent development of active disease. We investigated the safety and immunogenicity of a novel TB vaccine candidate, H4:IC31 (AERAS-404) that is composed of a fusion protein of M. tuberculosis antigens Ag85B and TB10.4 combined with an IC31® adjuvant.
BCG-vaccinated healthy subjects were immunized with various antigen (5, 15, 50, 150μg) and adjuvant (0, 100, 500nmol) doses of the H4:IC31 vaccine (n=106) or placebo (n=18) in two randomized, double-blind, placebo-controlled phase I studies conducted in a low TB endemic setting in Sweden and Finland. The subjects were followed for adverse events and CD4+ T cell responses.
H4:IC31 vaccination was well tolerated with a safety profile consisting of mostly mild to moderate self-limited injection site pain, myalgia, arthralgia, fever and post-vaccination inflammatory reaction at the screening tuberculin skin test injection site. The H4:IC31 vaccine elicited antigen-specific CD4+ T cell proliferation and cytokine production that persisted 18weeks after the last vaccination. CD4+ T cell expansion, IFN-γ production and multifunctional CD4+ Th1 responses were most prominent after two doses of H4:IC31 containing 5, 15, or 50μg of H4 in combination with the 500nmol IC31 adjuvant dose.
The novel TB vaccine candidate, H4:IC31, demonstrated an acceptable safety profile and was immunogenic, capable of triggering multifunctional CD4+ T cell responses in previously BCG-vaccinated healthy individuals. These dose-escalation trials provided evidence that the optimal antigen-adjuvant dose combinations are 5, 15, or 50μg of H4 and 500nmol of IC31.
Trial registration: ClinicalTrials.gov, NCT02066428 and NCT02074956.
Journal Article
From empiricism to rational design: a personal perspective of the evolution of vaccine development
The technological revolution in vaccination — from the empirical approach pioneered by Jenner and Pasteur to the recent developments in structural and reverse vaccinology, combined with synthetic biology — promises great hope for the development of safer and more effective vaccines against all infectious diseases.
Vaccination, which is the most effective medical intervention that has ever been introduced, originated from the observation that individuals who survived a plague or smallpox would not get the disease twice. To mimic the protective effects of natural infection, Jenner — and later Pasteur — inoculated individuals with attenuated or killed disease-causing agents. This empirical approach inspired a century of vaccine development and the effective prophylaxis of many infectious diseases. From the 1980s, several waves of new technologies have enabled the development of novel vaccines that would not have been possible using the empirical approach. The technological revolution in the field of vaccination is now continuing, and it is delivering novel and safer vaccines. In this Timeline article, we provide our views on the transition from empiricism to rational vaccine design.
Journal Article
First-in-human trial of the post-exposure tuberculosis vaccine H56:IC31 in Mycobacterium tuberculosis infected and non-infected healthy adults
H56:IC31 is a candidate tuberculosis vaccine comprising a fusion protein of Ag85B, ESAT-6 and Rv2660c, formulated in IC31 adjuvant. This first-in-human, open label phase I trial assessed the safety and immunogenicity of H56:IC31 in healthy adults without or with Mycobacterium tuberculosis (M.tb) infection.
Low dose (15μg H56 protein in 500nmol IC31) or high dose (50μg H56, 500nmol IC31) vaccine was administered intramuscularly thrice, at 56-day intervals. Antigen-specific T cell responses were measured by intracellular cytokine staining and antibody responses by ELISA.
One hundred and twenty-six subjects were screened and 25 enrolled and vaccinated. No serious adverse events were reported. Nine subjects (36%) presented with transient cardiovascular adverse events. The H56:IC31 vaccine induced antigen-specific IgG responses and Th1 cytokine-expressing CD4+ T cells. M.tb-infected vaccinees had higher frequencies of H56-induced CD4+ T cells than uninfected vaccinees. Low dose vaccination induced more polyfunctional (IFN-γ+TNF-α+IL-2+) and higher frequencies of H56-specific CD4+ T cells compared with high dose vaccination. A striking increase in IFN-γ-only-expressing CD4+ T cells, displaying a CD45RA−CCR7− effector memory phenotype, emerged after the second high-dose vaccination in M.tb-infected vaccinees. TNF-α+IL-2+ H56-specific memory CD4+ T cells were detected mostly after low-dose H56 vaccination in M.tb-infected vaccinees, and predominantly expressed a CD45RA−CCR7+ central memory phenotype. Our results support further clinical testing of H56:IC31.
Journal Article