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Vaccines against Chlamydophila pneumoniae.

C. pneumoniae is the third most common cause of community acquired pneumonia after infection due to the bacteria Streptococcus pneumoniae and Mycoplasma pneumoniae. This alone justifies vaccine development. However C. pneumoniae infection has also been associated with exacerbating a number of chronic human diseases, including asthma, obstructive pulmonary disease and atherosclerosis [see: C. pneumoniae and chronic disease]. Definitive evidence that C. pneumoniae plays a significant causal role in these conditions is  lacking. Any such evidence would be a further major boost to C. pneumoniae vaccine research. Nevertheless it is significant that a major vaccine company, Aventis-Pasteur, has chosen to target C. pneumoniae for vaccine development. I am grateful to Andrew Murdin of Aventis-Pasteur for providing me with the information below.

[Thumbnail: The Aventis-Pasteur approach to C. pneumoniae vaccine development].

Essentially, the Aventis-Pasteur team used the Incyte Pathoseq^Ò whole C. pneumoniae genome sequence, published by the Chlamydia genome project. From this database, the research team selected some 200 genes that they thought might possibly encode chlamydial components important for immunity.  Each of the corresponding gene sequences was cloned into another piece of virus-related DNA capable of causing the corresponding chlamydial protein encoded by the gene to be translated from the genetic code and expressed in animal cells. [An expression vector using a CMV promoter]. Each of these DNA preparations was then tested for its ability to protect Balb/C mice against a self-limiting C. pneumoniae lung infection. The mice were immunized at 0, 3 and 6 weeks with 50 micrograms of  DNA intranasally (nose drops) and with 100 micrograms by intramuscular injection. At week 8, the mice were challenged with either low (5 x 10⁴ inclusion forming units) or medium (5 x 10⁵ IFU) of C. pneumoniae. The amount of multiplication of chlamydiae in the lungs was determined 9 days after infection. Samples were also taken to determine if the mice were making a protective Th1 cell mediated immune response. 

In these mice, C. pneumoniae causes a self limiting lung infection of approximately 3 weeks duration, which is eventually cleared by their immune system. Previous recovery from infection with C. pneumoniae generated protective immunity demonstrated by an approximately 12-fold reduction in infectivity, while immunization with heat killed C. pneumoniae produced a 4-fold reduction. These were the parameters, then, against which the performance of the experimental gene vaccine constructs could be assessed. Vaccination with the carrier virus DNA vector alone, or with many  C. pneumoniae gene inserts was non protective. However gene inserts corresponding to C. pneumoniae major outer membrane protein (MOMP), and to other proteins such as the 60 KDa cysteine rich protein and to Npt1cp, an ADP/ATP translocase, protected against both the lower and the higher doses of C. pneumoniae challenge [Murdin et al., 2000a, b; See also Brunham & Zhang, 1999 and Brunham et al., 2000].

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References

Brunham, R. C. & Zhang, D-J. (1999). Transgene as vaccine for chlamydia. American Heart Journal 138, S519 - 522.

Brunham, R. C., Zhang, D. J., Yang, X. & McClarty, G. M. (2000). The potential for vaccine development against chlamydial infection and disease. Journal of Infectious Diseases 181, Suppl 3: S538-43.

Murdin, A. D., Dunn, P., Sodoyer, R., Wang, J., Caterini, J., Brunham, R. C., Aujame, L. & Oomen, R. (2000a). Use of a mouse lung challenge model to identify antigens protective against Chlamydia pneumoniae lung infection. Journal of Infectious Diseases 181 Suppl 3: S544 - 551.

Murdin,  A. D., Gellin, B., Brunham, R. C., Campbell, L. A., Christiansen, G., Deal, C. D., Jenson, H. B., Metcalf, B., Sankaran, B., Stephens, R. S. & Wilfert, C. (2000b). Collaborative multidisciplinary workshop report: progress toward a Chlamydia pneumoniae vaccine. Journal of Infectious Diseases 181 Suppl 3: S552 - 557.

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