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Vaccines
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Tuberculosis Vaccines
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Tuberculosis Vaccines

A special issue of Vaccines (ISSN 2076-393X).

Deadline for manuscript submissions: closed (31 October 2013) | Viewed by 38741

Special Issue Editors

Prof. Dr. Chinnaswamy Jagannath

E-Mail Website
Guest Editor
Department of Pathology and Laboratory Medicine, University of Texas Health Sciences Center, 6400 Fannin Street, MSB 2.200, Houston, TX 77030, USA
Interests: vaccines for tuberculosis; TLR signaling and adjuvants; Th1 immunity and T cells; Dendritic cells and macrophages-pathogen survival
Prof. Dr. Abu Salim Mustafa

E-Mail Website
Guest Editor
Department of Microbiology, Faculty of Medicine, Kuwait University, P.O. Box 24923, Safat 13110, Kuwait
Interests: tuberculosis; vaccines; immunodiagnosis; immuno-pathogenesis
Special Issues, Collections and Topics in MDPI journals

Special Issue Information

Dear Colleagues,

Tuberculosis is a major health problem of global concern. According to estimates from the World Health Organization, one-third of the world population is infected with Mycobacterium tuberculosis, over 9 million people develop active disease and 2 million people die of tuberculosis each year. To immunize against tuberculosis, routine vaccination with Mycobacterium bovis BCG is practiced in many countries. Although, BCG vaccine offers some protection against childhood tuberculosis and severe forms of the disease in adults, it has failed to provide consistent protection against pulmonary disease in adults, which is the major manifestation of tuberculosis. Investigators are attempting to develop improved vaccines against tuberculosis by genetic manipulation of BCG, identifying M. tuberculosis auxotroph and protein antigens as subunit vaccines, etc. This special issue on “Tuberculosis Vaccines”  will highlight leading developments in the vaccine technology, including but not limited to, genetically modified BCG, M. tuberculosis-derived vaccines, subunit (proteins/peptide, DNA and recombinant) vaccines, and their validation in animal models. Novel mechanisms of enhancing vaccine efficacy are also welcome including research on adjuvants and biomarkers of protection against tuberculosis. The special issue will be a mix of original research articles, and mini reviews. The main focus of this special issue is to present cutting edge research and recent developments in vaccines, which can prevent tuberculosis in mankind.

We look forward to reading your contributions

Prof. Dr. Chinnaswamy Jagannath
Prof. Dr. Abu Salim Mustafa
Guest Editors

Manuscript Submission Information

Manuscripts should be submitted online at www.mdpi.com by registering and logging in to this website. Once you are registered, click here to go to the submission form. Manuscripts can be submitted until the deadline. All submissions that pass pre-check are peer-reviewed. Accepted papers will be published continuously in the journal (as soon as accepted) and will be listed together on the special issue website. Research articles, review articles as well as short communications are invited. For planned papers, a title and short abstract (about 100 words) can be sent to the Editorial Office for announcement on this website.

Submitted manuscripts should not have been published previously, nor be under consideration for publication elsewhere (except conference proceedings papers). All manuscripts are thoroughly refereed through a single-blind peer-review process. A guide for authors and other relevant information for submission of manuscripts is available on the Instructions for Authors page. Vaccines is an international peer-reviewed open access monthly journal published by MDPI.

Please visit the Instructions for Authors page before submitting a manuscript. The Article Processing Charge (APC) for publication in this open access journal is 2700 CHF (Swiss Francs). Submitted papers should be well formatted and use good English. Authors may use MDPI's English editing service prior to publication or during author revisions.

Keywords

  • genetically modified BCG
  • M. tuberculosis-derived vaccines
  • subunit and peptide-based vaccines
  • DNA vaccines
  • recombinant-vector based vaccines
  • adjuvants for vaccine delivery
  • biomarkers of protection and novel mechanisms for enhancing vaccine efficacy

Published Papers (4 papers)

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Research

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494 KiB  
Article
Nonclinical Development of BCG Replacement Vaccine Candidates
by Kamalakannan Velmurugan, Leander Grode, Rosemary Chang, Megan Fitzpatrick, Dominick Laddy, David Hokey, Steven Derrick, Sheldon Morris, David McCown, Reginald Kidd, Martin Gengenbacher, Bernd Eisele, Stefan H.E. Kaufmann, John Fulkerson and Michael J. Brennan
Vaccines 2013, 1(2), 120-138; https://doi.org/10.3390/vaccines1020120 - 16 Apr 2013
Cited by 26 | Viewed by 10632
Abstract
The failure of current Mycobacterium bovis bacille Calmette–Guérin (BCG) vaccines, given to neonates to protect against adult tuberculosis and the risk of using these live vaccines in HIV-infected infants, has emphasized the need for generating new, more efficacious and safer replacement vaccines. With [...] Read more.
The failure of current Mycobacterium bovis bacille Calmette–Guérin (BCG) vaccines, given to neonates to protect against adult tuberculosis and the risk of using these live vaccines in HIV-infected infants, has emphasized the need for generating new, more efficacious and safer replacement vaccines. With the availability of genetic techniques for constructing recombinant BCG (rBCG) strains containing well-defined gene deletions or insertions, new vaccine candidates are under evaluation at both the preclinical and clinical stages of development. Since most BCG vaccines in use today were evaluated in clinical trials decades ago and are produced by outdated processes, the development of new BCG vaccines offers a number of advantages that include a modern well-defined manufacturing process along with state-of-the-art evaluation of safety and efficacy in target populations. We provide a description of the preclinical development of two novel rBCGs, VPM1002 that was constructed by adding a modified hly gene coding for the protein listeriolysin O (LLO) from Listeria monocytogenes and AERAS-422, which carries a modified pfoA gene coding for the protein perfringolysin O (PFO) from Clostridium perfringens, and three genes from Mycobacterium tuberculosis. Novel approaches like these should be helpful in generating stable and effective rBCG vaccine candidates that can be better characterized than traditional BCG vaccines. Full article
(This article belongs to the Special Issue Tuberculosis Vaccines)
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2512 KiB  
Article
A Modified Bacillus Calmette-Guérin (BCG) Vaccine with Reduced Activity of Antioxidants and Glutamine Synthetase Exhibits Enhanced Protection of Mice despite Diminished in Vivo Persistence
by Carolyn M. Shoen, Michelle S. DeStefano, Cynthia C. Hager, Kyi-Toe Tham, Miriam Braunstein, Alexandria D. Allen, Hiriam O. Gates, Michael H. Cynamon and Douglas S. Kernodle
Vaccines 2013, 1(1), 34-57; https://doi.org/10.3390/vaccines1010034 - 11 Jan 2013
Cited by 4 | Viewed by 9280
Abstract
Early attempts to improve BCG have focused on increasing the expression of prominent antigens and adding recombinant toxins or cytokines to influence antigen presentation. One such modified BCG vaccine candidate has been withdrawn from human clinical trials due to adverse effects. BCG was [...] Read more.
Early attempts to improve BCG have focused on increasing the expression of prominent antigens and adding recombinant toxins or cytokines to influence antigen presentation. One such modified BCG vaccine candidate has been withdrawn from human clinical trials due to adverse effects. BCG was derived from virulent Mycobacterium bovis and retains much of its capacity for suppressing host immune responses. Accordingly, we have used a different strategy for improving BCG based on reducing its immune suppressive capacity. We made four modifications to BCG Tice to produce 4dBCG and compared it to the parent vaccine in C57Bl/6 mice. The modifications included elimination of the oxidative stress sigma factor SigH, elimination of the SecA2 secretion channel, and reductions in the activity of iron co-factored superoxide dismutase and glutamine synthetase. After IV inoculation of 4dBCG, 95% of vaccine bacilli were eradicated from the spleens of mice within 60 days whereas the titer of BCG Tice was not significantly reduced. Subcutaneous vaccination with 4dBCG produced greater protection than vaccination with BCG against dissemination of an aerosolized challenge of M. tuberculosis to the spleen at 8 weeks post-challenge. At this time, 4dBCG-vaccinated mice also exhibited altered lung histopathology compared to BCG-vaccinated mice and control mice with less well-developed lymphohistiocytic nodules in the lung parenchyma. At 26 weeks post-challenge, 4dBCG-vaccinated mice but not BCG-vaccinated mice had significantly fewer challenge bacilli in the lungs than control mice. In conclusion, despite reduced persistence in mice a modified BCG vaccine with diminished antioxidants and glutamine synthetase is superior to the parent vaccine in conferring protection against M. tuberculosis. The targeting of multiple immune suppressive factors produced by BCG is a promising strategy for simultaneously improving vaccine safety and effectiveness. Full article
(This article belongs to the Special Issue Tuberculosis Vaccines)
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Review

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723 KiB  
Review
Novel GMO-Based Vaccines against Tuberculosis: State of the Art and Biosafety Considerations
by Amaya Leunda, Aline Baldo, Martine Goossens, Kris Huygen, Philippe Herman and Marta Romano
Vaccines 2014, 2(2), 463-499; https://doi.org/10.3390/vaccines2020463 - 16 Jun 2014
Cited by 3 | Viewed by 11607
Abstract
Novel efficient vaccines are needed to control tuberculosis (TB), a major cause of morbidity and mortality worldwide. Several TB vaccine candidates are currently in clinical and preclinical development. They fall into two categories, the one of candidates designed as a replacement of the [...] Read more.
Novel efficient vaccines are needed to control tuberculosis (TB), a major cause of morbidity and mortality worldwide. Several TB vaccine candidates are currently in clinical and preclinical development. They fall into two categories, the one of candidates designed as a replacement of the Bacille Calmette Guérin (BCG) to be administered to infants and the one of sub-unit vaccines designed as booster vaccines. The latter are designed as vaccines that will be administered to individuals already vaccinated with BCG (or in the future with a BCG replacement vaccine). In this review we provide up to date information on novel tuberculosis (TB) vaccines in development focusing on the risk assessment of candidates composed of genetically modified organisms (GMO) which are currently evaluated in clinical trials. Indeed, these vaccines administered to volunteers raise biosafety concerns with respect to human health and the environment that need to be assessed and managed. Full article
(This article belongs to the Special Issue Tuberculosis Vaccines)
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Other

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447 KiB  
Concept Paper
Perspectives for Developing New Tuberculosis Vaccines Derived from the Pathogenesis of Tuberculosis: I. Basic Principles, II. Preclinical Testing, and III. Clinical Testing
by Arthur M. Dannenberg and Bappaditya Dey
Vaccines 2013, 1(1), 58-76; https://doi.org/10.3390/vaccines1010058 - 25 Jan 2013
Viewed by 6431
Abstract
Part I. Basic Principles. TB vaccines cannot prevent establishment of the infection. They can only prevent an early pulmonary tubercle from developing into clinical disease. A more effective new vaccine should optimize both cell-mediated immunity (CMI) and delayed-type hypersensitivity (DTH) better than any [...] Read more.
Part I. Basic Principles. TB vaccines cannot prevent establishment of the infection. They can only prevent an early pulmonary tubercle from developing into clinical disease. A more effective new vaccine should optimize both cell-mediated immunity (CMI) and delayed-type hypersensitivity (DTH) better than any existing vaccine. The rabbit is the only laboratory animal in which all aspects of the human disease can be reproduced: namely, the prevention of most primary tubercles, the arrestment of most primary tubercles, the formation of the tubercle’s solid caseous center, the liquefaction of this center, the formation of cavities and the bronchial spread of the disease. In liquefied caseum, virulent tubercle bacilli can multiply extracellularly, especially in the liquefied caseum next to the inner wall of a cavity where oxygen is plentiful. The bacilli in liquefied caseum cannot be reached by the increased number of activated macrophages produced by TB vaccines. Therefore, new TB vaccines will have little or no effect on the extracellular bacillary growth within liquefied caseum. TB vaccines can only increase the host’s ability to stop the development of new TB lesions that arise from the bronchial spread of tubercle bacilli from the cavity to other parts of the lung. Therefore, effective TB vaccines do not prevent the reactivation of latent TB. Such vaccines only control (or reduce) the number of metastatic lesions that result after the primary TB lesion was reactivated by the liquefaction process. (Note: the large number of tubercle bacilli growing extracellularly in liquefied caseum gives rise to mutations that enable antimicrobial resistance—which is a major reason why TB still exists today). Part II. Preclinical Testing. The counting of grossly visible tubercles in the lungs of rabbits after the inhalation of virulent human-type tubercle bacilli is the most pertinent preclinical method to assess the efficacy of new TB vaccines (because an effective vaccine will stop the growth of developing tubercles before while they are still microscopic in size). Unfortunately, rabbits are rarely used in preclinical vaccine trials, despite their relative ease of handling and human-like response to this infection. Mice do not generate an effective DTH response, and guinea pigs do not generate an effective CMI response. Only the rabbits and most humans can establish the proper amount of DTH and CMI that is necessary to contain this infection. Therefore, rabbits should be included in all pre-clinical testing of new TB vaccines. New drugs (and/or immunological procedures) to reduce liquefaction and cavity formation are urgently needed. A simple intradermal way to select such drugs or procedures is described herein. Part III. Clinical Testing. Vaccine trials would be much more precise if the variations in human populations (listed herein) were taken into consideration. BCG and successful new TB vaccines should always increase host resistance to TB in naive subjects. This is a basic immunological principle. The efficacies of new and old TB vaccines are often not recognized, because these variations were not identified in the populations evaluated. Full article
(This article belongs to the Special Issue Tuberculosis Vaccines)
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