Nonclinical Development of BCG Replacement Vaccine Candidates.
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 Since most BCG vaccines in use today were evaluated in clinical trials decades ago and are produced by outdated processes, the development of new BCG vaccines offers a number of advantages that include a modern well-defined manufacturing process along with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.
Aeras, Rockville, MD 20850, USA. kvelmurugan@aeras.org.
Kamalakannan
K
Velmurugan
Vakzine Projekt Management GmbH, Mellendorferstrasse 9, 30625 Hannover, Germany.
Leander
L
Grode
Aeras, Rockville, MD 20850, USA.
Rosemary
R
Chang
Aeras, Rockville, MD 20850, USA.
Megan
M
Fitzpatrick
Aeras, Rockville, MD 20850, USA.
Dominick
D
Laddy
Aeras, Rockville, MD 20850, USA.
David
D
Hokey
Center for Biologics Evaluation and Research, Food and Drug Administration, Bethesda, MD 20892, USA.
Steven
S
Derrick
Center for Biologics Evaluation and Research, Food and Drug Administration, Bethesda, MD 20892, USA.
Sheldon
S
Morris
Aeras, Rockville, MD 20850, USA.
David
D
McCown
Aeras, Rockville, MD 20850, USA.
Reginald
R
Kidd
Max Planck Institute for Infection Biology, Department of Immunology, Charitéplatz, 110117 Berlin, Germany.
Martin
M
Gengenbacher
Vakzine Projekt Management GmbH, Mellendorferstrasse 9, 30625 Hannover, Germany.
Bernd
B
Eisele
Max Planck Institute for Infection Biology, Department of Immunology, Charitéplatz, 110117 Berlin, Germany.
Stefan H E
SH
Kaufmann
Aeras, Rockville, MD 20850, USA.
John
J
Fulkerson
Aeras, Rockville, MD 20850, USA.
Michael J
MJ
Brennan
Mycobacterium tuberculosis; live vaccines; recombinant BCG; tuberculosis