Recombinant BCG as a candidate oral vaccine vector

• Published in: Research in microbiology Vol. 141; no. 7-8; pp. 931 - 939
• Main Authors: Barletta, R.G., Snapper, B., Cirillo, J.D., Connell, N.D., Kim, D.D., Jacobs, W.R., Bloom, B.R.
• Format: Journal Article Conference Proceeding
• Language: English
• Published: Paris Elsevier Masson SAS 01.09.1990; Elsevier
• Subjects: Administration, Oral; Animals; Bacille Calmette-Guerin, Recombinant oral vaccine, Shuttle vector; Bacteriology; BCG Vaccine - administration & dosage; BCG Vaccine - genetics; Biological and medical sciences; Fundamental and applied biological sciences. Psychology; Genes, Bacterial; Genetic Vectors; Humans; Microbiology; Mycobacterium bovis - genetics; Mycobacterium bovis - immunology; Plasmids; Vaccines, antisera, therapeutical immunoglobulins and monoclonal antibodies; Vaccines, Synthetic - administration & dosage; Vaccines, Synthetic - genetics; β-Galactosidase, Mycobacteria; β-Galactosidase, Mycobacteria; Bacille Calmette-Guerin, Recombinant oral vaccine, Shuttle vector
• ISSN: 0923-2508; 1769-7123
• DOI: 10.1016/0923-2508(90)90132-A

Bacille Calmette-Guerin (BCG), currently the most widely used vaccine in the world, was originally administered for many years as an oral vaccine. The low frequency of serious complications, inexpensive production, and adjuvanticity make BCG an ideal candidate for a recombinant vaccine vehicle. Although mycobacteria are slow growing and not yet well characterized genetically, we have recently developed technology for the genetic manipulation of BCG and other mycobacteria. Phage and plasmid systems based on a shuttle strategy to manipulate DNA in Escherichia coli and transfer it to mycobacteria have been developed. We have established that the aminoglycoside phosphotransferase gene can be used as an effective selectable marker in the mycobacteria and that a foreign antigen from Mycobacterium leprae can be expressed in BCG. Furthermore, a thorough analysis of mycobacterial expression sequences has been undertaken to optimize the expression of foreign antigens in BCG. We constructed an expression probe shuttle plasmid with β-galactosidase as reporter gene, and have used it successfully to identify multiple mycobacteriophage DNA sequences with varying levels of constitutive or regulable promotor activity. Further genetic advances required for development of recombinant BCG into an effective recombinant vaccine vehicle, including possibilities for oral administration, are adumbrated.