Evaluation of vaccines in the EU TB Vaccine Cluster using a guinea pig aerosol infection model of tuberculosis

Williams, Ann; Hatch, Graham; Clark, Simon; Gooch, Karen E.; Hatch, Kim A.; Hall, G.A.; Huygen, Kris; Ottenhoff, Tom H. M.; Franken, Kees L. M. C.; Andersen, Peter; Doherty, T. Mark; Kaufmann, Stefan H. E.; Grode, Leander; Seiler, Peter; Martín, Carlos; Gicquel, Brigitte; Cole, Stewart T.; Brodin, Priscille; Pym, Alexander S.; Dalemans, Wilfried; Cohen, Joe; Lobet, Yves; Goonetilleke, Nilu; McShane, Helen; Hill, Adrian V. S.; Parish, Tanya; Smith, Debbie A.; Stoker, Neil G.; Lowrie, Douglas B.; Källenius, Gunilla; Svenson, Stefan B.; Pawłowski, Andrzej; Blake, Karen; Marsh, Philip

doi:10.1016/j.tube.2004.09.009

Cited by 153 publications

(104 citation statements)

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“…Cationic liposomes are very efficient delivery systems for protein antigens and have recently been tested and found highly efficient for the delivery of Ag85B-ESAT-6 in various animal models of TB [30,31]. We therefore examined the effect of liposome delivery of the adenovirus constructs on the immune response induced.…”

Section: Liposome Delivery Of Adenovirus Potentiates the T Cell Respomentioning

confidence: 99%

Alteration of epitope recognition pattern in Ag85B and ESAT‐6 has a profound influence on vaccine‐induced protection against Mycobacterium tuberculosis

et al. 2006

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To analyze the effect of vaccine delivery systems on antigen recognition and vaccine efficacy, we compared immune responses in mice immunized either with an adenovirus vector expressing a fusion of Ag85B and ESAT-6 or with the recombinant fusion protein in a liposomal adjuvant. Both vaccines induced high levels of antigen-specific IFN-c production. The adjuvanted protein vaccine induced primarily a CD4 T cell response directed to the epitope Ag85B 241-255 and gave efficient protection against subsequent Mycobacterium tuberculosis infection. In contrast, the adenoviral construct induced a strong CD8 response predominantly targeted to the epitope ESAT-6 15-29 and no significant protection against infection. Vaccination with the protein vaccine resulted in highly accelerated recall of Ag85B 241-255 -specific T cells immediately post M. tuberculosis challenge whereas the ESAT-6 15-29 epitope was barely recognized during infection. Delivery of the viral construct in cationic liposomes switched the immune response to a protective one dominated by CD4 T cells targeted to the Ag85B [241][242][243][244][245][246][247][248][249][250][251][252][253][254][255] epitope. These data demonstrate that the nature of the T cell response to a vaccine antigen is more important than its magnitude with respect to protective efficacy and that vaccine-mediated changes in immunodominance can result in T cell responses of limited relevance during the natural infection.

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Section: Liposome Delivery Of Adenovirus Potentiates the T Cell Respomentioning

confidence: 99%

Alteration of epitope recognition pattern in Ag85B and ESAT‐6 has a profound influence on vaccine‐induced protection against Mycobacterium tuberculosis

et al. 2006

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“…To enhance the activity of mutant strains, deletion specifically affecting the bacilli's ability to persist in host tissues without dramatically impairing basic biological processes have been developed. An M. tuberculosis mutant for genes involved in the panthotenate biosynthesis has been shown to be safe even in immunocompromised animals, but still capable of persisting in host tissues without causing significant damage [29].…”

Section: Attenuated M Tuberculosis Mutantsmentioning

confidence: 99%

“…Similarly, a recombinant poly-protein (Mtb72f) based on two antigens, Mtb39A and Mtb32C, was shown to be highly immunogenic and capable of inducing a level of protection equivalent to those provided by BCG, both in the mouse and guinea pig models of infection [43]. The promising results obtained with Mtb72F and Ag85B-Esat6 (Hybrid-1) in the pre-clinical animal models paved the way to human clinical trials [29]. Moreover, attempts are being made to develop new and improved recombinant fusion proteins, such as a fusion between Ag85B and Mtb10.4 (HyVac-4) that would not affect the use of T cell restimulation assays currently used to distinguish people with M. tuberculosis infection from those immunized with BCG, such as the ESAT-6 antigen [44].…”

Section: Secreted and Highly Immunogenic Antigens Of Unknown Functionmentioning

confidence: 99%

The quest for a new vaccine against tuberculosis

Delogu

Fadda

2009

J Infect Dev Ctries

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Tuberculosis (TB) is still one of the deadliest human diseases, killing 1,6 million people each year, mostly in developing countries. The vaccine currently used, Bacille Calmette and Guerin (BCG), is effective in preventing the most severe disseminated forms of disease in children and newborns, but its efficacy against active TB in adults has been challenged by several clinical studies. It is a common opinion that only the development of a new and more effective vaccine against TB would significantly ease the pandemic. In the last few years, the search for a new vaccine has gained a new momentum. New live and attenuated strains of M. tuberculosis, improved recombinant BCG strains and subunit vaccines have been tested in preclinical animal models, and some of them showed promising results. Unfortunately, the lack of immunological correlates of protection makes very difficult to anticipate or foresee the efficacy of any of these new vaccines and only phase III clinical trials, that are expected to start in 2009 and last few years, will tell us the real value of these new prophylactic tools. This review highlights the different strategies that are being implemented for the development of an improved vaccine against TB, the rationale behind them and the potential and feasible vaccination schedules that could be implemented.

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“…That bottleneck was effectively circumvented by the development of a US NIH-funded contract to test vaccines without cost for any investigator in the world. Since the inception of that testing service and a similar vaccine screening program funded by the EU TB Vaccine Cluster, hundreds of vaccine candidates have been tested in mice and guinea pigs [20,21]. During that time, four important paradigm shifts have occurred.…”

Section: When Is a Model Not A Model?mentioning

confidence: 99%

TB vaccines: the paradigms they are a-shifting

McMurray

2009

Expert Review of Vaccines

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"The urgency to license a new TB vaccine has driven a worldwide effort over the past 20 years involving basic scientists, public and private funding agencies, regulatory bodies, and disease control experts in high-burden countries."Traditional roadblocks to effective TB control (e.g., lack of attention to the disease, lack of resources, antiquated diagnostic tests, lack of patient compliance with therapy and a huge reservoir of persistently infected individuals) have been compounded by the terrible synergy between TB and HIV, and the development of almost untreatable multi-and extensively drug-resistant strains of Mycobacterium tuberculosis [1]. Case-finding and chemotherapy employing the Directly Observed Treatment, Short-course strategy, and several promising new TB drugs currently in the pipeline, will undoubtedly continue to have a significant impact on TB incidence [2,3]. However, it is clear that an effective vaccine is essential if TB is to be controlled as rapidly as possible [4][5][6]. The urgency to license a new TB vaccine has driven a worldwide effort over the past 20 years involving basic scientists, public and private funding agencies, regulatory bodies, and disease control experts in highburden countries [7]. That effort has been shaped at various stages by several paradigms that reflected the current understanding of the type of vaccine that would be needed, the manner in which vaccines should be evaluated for efficacy in animal models, the process by which preclinical development of vaccines would occur, the design of clinical trials, and the public and private organizations that would participate in the process. Almost without exception, those paradigms have shifted as the understanding of vaccine-induced protection has improved, an appreciation for the biological relevance of certain animal models of TB has grown, new strategies for organizing and funding preclinical development and human trials have emerged, and the realities of testing and using TB vaccines in diverse high-burden populations have become apparent. Variety is the spice of lifeIn general, the induction of protective cell-mediated immunity is much more challenging than inducing a protective antibody response, a fact which has complicated the search for a better TB vaccine. The current vaccine, bacillus CalmetteGuérin (BCG), is a living, attenuated strain (actually several different strains) of Mycobacterium bovis, which has served as a model for new TB vaccines and a gold standard for their evaluation in animal models [8]. BCG has many characteristics that recommend it as a platform for new TB vaccines, and several of the promising new vaccines utilize recombinant BCG strains overexpressing the genes for several mycobacterial antigens [9,10]. However, the fact that BCG does not seem to protect against adult pulmonary TB in some high-burden settings has stimulated the search for other types of TB vaccines. The traditional approach of using purified components of the bacterium together with an effective adjuvant has been modernize...

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Evaluation of vaccines in the EU TB Vaccine Cluster using a guinea pig aerosol infection model of tuberculosis

Cited by 153 publications

References 20 publications

Alteration of epitope recognition pattern in Ag85B and ESAT‐6 has a profound influence on vaccine‐induced protection against Mycobacterium tuberculosis

Alteration of epitope recognition pattern in Ag85B and ESAT‐6 has a profound influence on vaccine‐induced protection against Mycobacterium tuberculosis

The quest for a new vaccine against tuberculosis

TB vaccines: the paradigms they are a-shifting

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