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

Nonclinical Development of BCG Replacement Vaccine Candidates

Received: 28 February 2013; in revised form: 3 April 2013 / Accepted: 8 April 2013 / Published: 16 April 2013
(This article belongs to the Special Issue Tuberculosis Vaccines)
This is an open access article distributed under the Creative Commons Attribution License which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.
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 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 Since most BCG vaccines in use today were evaluated in clinical trials decades ago and are produced by outdated processes, the development of new BCG vaccines offers a number of advantages that include a modern well-defined manufacturing process along with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.
Keywords: tuberculosis; live vaccines; Mycobacterium tuberculosis; recombinant BCG
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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.

AMA 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 SH, Fulkerson J, Brennan MJ. Nonclinical Development of BCG Replacement Vaccine Candidates. Vaccines. 2013; 1(2):120-138.

Chicago/Turabian Style

Velmurugan, Kamalakannan; Grode, Leander; Chang, Rosemary; Fitzpatrick, Megan; Laddy, Dominick; Hokey, David; Derrick, Steven; Morris, Sheldon; McCown, David; Kidd, Reginald; Gengenbacher, Martin; Eisele, Bernd; Kaufmann, Stefan H.; Fulkerson, John; Brennan, Michael J. 2013. "Nonclinical Development of BCG Replacement Vaccine Candidates." Vaccines 1, no. 2: 120-138.

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