Next Article in Journal
Kaiser Permanente Vaccine Study Center: Highlights of 2009–2012
Next Article in Special Issue
Novel GMO-Based Vaccines against Tuberculosis: State of the Art and Biosafety Considerations
Previous Article in Journal
Change in Hepatitis A Seroprevalence among U.S. Children and Adolescents: Results from the National Health and Nutrition Examination Survey 2003–2006 and 2007–2010
Previous Article in Special Issue
Perspectives for Developing New Tuberculosis Vaccines Derived from the Pathogenesis of Tuberculosis: I. Basic Principles, II. Preclinical Testing, and III. Clinical Testing
Article Menu

Export Article

Open AccessArticle
Vaccines 2013, 1(2), 120-138; doi:10.3390/vaccines1020120

Nonclinical Development of BCG Replacement Vaccine Candidates

Aeras, Rockville, MD 20850, USA
Vakzine Projekt Management GmbH, Mellendorferstrasse 9, 30625 Hannover, Germany
Center for Biologics Evaluation and Research, Food and Drug Administration, Bethesda, MD 20892, USA
Max Planck Institute for Infection Biology, Department of Immunology, Charitéplatz, 110117 Berlin, Germany
Author to whom correspondence should be addressed.
Received: 28 February 2013 / Revised: 3 April 2013 / Accepted: 8 April 2013 / Published: 16 April 2013
(This article belongs to the Special Issue Tuberculosis Vaccines)
View Full-Text   |   Download PDF [494 KB, uploaded 16 April 2013]   |  


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 Since most BCG vaccines in use today were evaluated in clinical trials decades ago and are produced by outdated processes, the development of new BCG vaccines offers a number of advantages that include a modern well-defined manufacturing process along with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. View Full-Text
Keywords: tuberculosis; live vaccines; Mycobacterium tuberculosis; recombinant BCG tuberculosis; live vaccines; Mycobacterium tuberculosis; recombinant BCG

This is an open access article distributed under the Creative Commons Attribution License (CC BY 3.0).

Scifeed alert for new publications

Never miss any articles matching your research from any publisher
  • Get alerts for new papers matching your research
  • Find out the new papers from selected authors
  • Updated daily for 49'000+ journals and 6000+ publishers
  • Define your Scifeed now

SciFeed Share & Cite This Article

MDPI and ACS Style

Velmurugan, K.; Grode, L.; Chang, R.; Fitzpatrick, M.; Laddy, D.; Hokey, D.; Derrick, S.; Morris, S.; McCown, D.; Kidd, R.; Gengenbacher, M.; Eisele, B.; Kaufmann, S.H.; Fulkerson, J.; Brennan, M.J. Nonclinical Development of BCG Replacement Vaccine Candidates. Vaccines 2013, 1, 120-138.

Show more citation formats Show less citations formats

Related Articles

Article Metrics

Article Access Statistics



[Return to top]
Vaccines EISSN 2076-393X Published by MDPI AG, Basel, Switzerland RSS E-Mail Table of Contents Alert
Back to Top