Genetic diversity of Chlamydia pecorum strains in wild koala locations across Australia and the implications for a recombinant C. pecorum major outer membrane protein based vaccine
Kollipara, A, Polkinghorne, A, Wan, C, Kanyoka, P, Hanger, J, Loader, J, Callaghan, J, Bell, A, Ellis, W, Fitzgibbon, S, Melzer, A, Beagley, K & Timms, P 2013, Veterinary Microbiology, vol. 167, pp. 513-522.
The genetic diversity of Chlamydia pecorum strains in koalas has limited the production of an effective cross-strain vaccine. By examining C. pecorum isolates from koalas across their range, the most common major outer membrane protein (MOMP) amino type F was suggested to be a prime candidate for recombinant C. pecorum vaccine development.
C. pecorum infection is extremely common in koalas and contributes to a significant proportion of koala admittance to veterinary hospitals. The aim of this study was to characterise the genetic diversity of C. pecorum ompA gene in wild koala populations to determine the impact of variation of full length MOMP sequences on C. pecorum vaccine development. 16S rRNA screening with quantitative PCR (qPCR) was conducted on the samples and revealed that 45% of koalas tested positive for C. pecorum infection. From the positive samples, serotyping of the C. pecorum ompA gene and sequence analysis identified 10 full length MOMP amino type sequences, with MOMP amino type F being the most common. Analysis of the 363 ompA coding sites (codons) identified 23 non-synonymous mutations, 14 of which were present in the variable domains (VDs); while 106 codons were identified to be synonymous mutations, 97 of which were present in the conserved domains (CDs). When T and B cell epitopes were predicted using the MOMP sequences, B cell epitopes were found to be highly variable across C. pecorum strains, with four out of six predicted B cell epitopes found in the VDs; in contrast, all 10 predicted T cell epitopes were found in the CDs.
Previous studies have reported the genetic diversity of the ompA gene based on the analysis of partial sequence within the VDs, limiting vaccine development to single-strain specificity, due to the highly variable nature of the full length ompA gene. The findings of this study suggest that the high level of mutation in B cell epitopes across different C. pecorum strains were a result of selection pressure from the host immunological response, despite having high affinity with host antibodies. Taken together with the high level of conservation of T cell epitopes, even across multiple animal C. pecorum isolates, these findings suggest that a recombinant vaccine based on full length MOMP sequence could have high binding affinity while potentially inducing strong cross-host and -strain reactivity.
The current study has implications for the current vaccine development landscape. Identification of T and B cell epitopes in the CDs and VDs of MOMP may allow for the development of an appropriate C. pecorum recom binant vaccine. This recombinant vaccine could be based on the MOMP amino type F, as it was found to be the most common across koala populations and is related to multiple C. pecorum isolates.
Summarised by Daniel Chew
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