Mice Protected by Vaccine Based on Genetically Weakened Pneumonia Bacteria

It has a range of biological activities including the ability to lyse and interfere with the function of cells and soluble molecules of the immune system. Secreted pneumolysin aids the bacteria during colonization, by facilitating adherence to the host, during invasion by damaging host cells, and during infection by interfering with the host immune response.

Investigators at the Albert Einstein College of Medicine (New York, NY, USA) used a previously described method of controlling gene expression with computer-based gene design and de novo DNA synthesis to attenuate the virulence of Streptococcus pneumoniae. They produced two weakened S. pneumoniae serotype 3 (SP3) strains in which the pneumolysin gene (ply) was recoded with underrepresented codon pairs while retaining its amino acid sequence.

Results of studies conducted with these modified strains were published in the February 21, 2011, online edition of the Journal of Infectious Diseases. They revealed that expression of ply and production of pneumolysin by the recoded SP3 strains were decreased, and the recoded SP3 strains were less virulent in mice than the wild-type SP3 strain or a delta-ply SP3 strain. The least virulent recoded strain induced a markedly reduced inflammatory response in the lungs compared with the wild type or delta-ply strain. Despite the reduced inflammatory response engendered by the mutated bacteria, an immune response was generated that protected the mice from subsequent challenge with the wild-type strain of S. pneumoniae.

"Our idea was to design a live vaccine that would stimulate the immune system sufficiently to ward off disease but would not lead to the severely damaging inflammatory response that this strain can cause,” said first author Dr. J. Robert Coleman, a postdoctoral fellow in microbiology and immunology at the Albert Einstein College of Medicine. "The novelty of this approach lies in the fact that the gene's expression would be reduced, but not eliminated. Previous approaches to genetic regulation of virulence relied on knocking out genes, which eliminates their expression completely.”

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