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Is there protective immunity?

[Thumbnail: Summary of evidence suggesting vaccination is feasible].

Briefly, the evidence is as follows. 1) Active trachoma is a childhood disease, suggesting that repeated exposure to infection in an endemic area eventually lead to immunity. Similarly, for the genital tract, isolation of C. trachomatis decreases significantly with age independently of diminished sexual activity, suggesting that exposure leads to moderate protection. This might explain why chlamydial genital tract infection is relatively uncommon in groups repeatedly exposed to infection, notably commercial sex workers. It would also explain why C. trachomatis infections are generally limited to the superficial mucosae and why shedding tends to resolve if infection is left untreated. However, this limited protection must be short lived as chlamydiae are reportedly isolated more often at a second isolation attempt if the interval between cultures is longer than six months. 3) Empirical attempts to prevent ocular infection by vaccination with crude, whole preparations of C. trachomatis achieved limited success in some studies in trachoma patients and in blind volunteers, although protection was short-lived. 4) Limited protection (see later) has been achieved in experimental animals following vaccination with whole dead chlamydiae, or with the chlamydial major outer membrane protein (MOMP). Both live and dead C. abortus vaccines are or have been used  for the prevention of ovine abortion. 5) Antigenic variation is a common method by which micro-organisms escape the host immune response. In the case of MOMP, although antigenic drift and shift occur, there is no convincing evidence this is likely to frustrate vaccine development, despite the occurrence of intraserovar recombination [Hayes et al., 1994; Millman et al., 2001]. The discovery of the polymorphic membrane proteins by Longbottom et al., 1996 & 1998 opened up the possibility of a new series of proteins in the chlamydial envelope with vaccine potential. Subsequently, genomic sequencing [Stephens et al., 1998] revealed the range and complexity of these proteins. It is understood that polymorphic membrane proteins are the basis of the experimental TRACVAX C. trachomatis vaccine of Antex Biologics Incorporated which it was announced  [May 21st 2002] is going to phase 1 clinical trial [see: news]. 

There are a number of reasons for believing that the development of vaccines against the chlamydiae is not going to be easy. These are summarized in the slide below:

[Thumbnail: Developing a vaccine is not going to be easy].

[MEW] June 2002

NEXT: The basis of protective immunity against chlamydiae.

References.

Hayes, L. J., Yearsley, P., Treharne, J. D., Ballard, R., Fehler, G. H. & Ward, M. E. (1994). Evidence for naturally occurring recombination in the gene encoding the major outer membrane protein of lymphogranuloma venereum isolates of C. trachomatis. Infection and  Immunity 62, 5659 - 5663. [Clear cross over point in VS2 subsequently confirmed by Millman et al., 2001]

Longbottom, D., Russell, M., Jones, G. E., Lainson, F. A. & Herring, A. J. (1996). Identification of a multigene family coding for the 90 kDa proteins of the ovine abortion subtype of Chlamydia psittaci. FEMS Microbiology Letters 142, 277 - 281.[First discovery of the polymorphic membrane proteins and initial recognition of their potential as protective antigens].

Longbottom, D., Russell, M., Dunbar, S. M., Jones, G. E. & Herring, A. J. (1998a). Molecular cloning and characterization of the genes coding for the highly immunogenic cluster of 90-kilodalton envelope proteins from the Chlamydia psittaci subtype that causes abortion in sheep. Infection and Immunity 66, 1317 - 1324. Full article   .

Millman, K. L., Tavare, S. & Dean, D. (2001). Recombination in the ompA gene but not the omcB gene of Chlamydia contributes to serovar-specific differences in tissue tropism, immune surveillance, and persistence of the organism. Journal of Bacteriology 183, 5997 - 6008. Full article [Excellent and thoughtful study. Good literature review].

Stephens, R. S., Kalman, S., Lammel, C. et al., (1998). Genome sequence of an obligate intracellular pathogen of humans: Chlamydia trachomatis. Science 282, 754 - 759. + [The first genomic sequence, and high quality]