Development of a chlamydial vaccine for koalas (Phascolarctos cinereus)

Abstract

The koala (Phascolarctos cinereus) is an iconic arboreal marsupial and the only surviving member of the Family Phascolarctidae. Chlamydiosis in koalas causes significant morbidity and mortality and adds to the detrimental effects of anthropological changes such as deforestation, bush fire, motor vehicle trauma and dog attacks. Mathematical modelling suggests that by reducing the negative effects of chlamydiosis, koala population in decline could well be saved. Chlamydia is an obligate intracellular pathogen of both humans and animals and C.pecorum is the most common and serious species affecting koalas. Ocular infections in koalas cause kerato-conjunctivitis leading to blindness, whereas uro-genital infections cause thickening of the bladder wall, incontinence and fibrosis in the uterine tract.While antibiotics are the current leading curative measures, these are ineffective for severe chlamydiosis and can also affect the intestinal micro flora and the overall health of the animals. The asymptomatic nature of the chlamydial infection and the variable effects of the long term antibiotic treatment heighten the importance of developing a suitable antichlamydial vaccine.The overall goal of developing an effective koala -Chlamydia vaccine requires a focus on exploring suitable vaccine antigens with immune stimulating adjuvants, to produce a long lasting cellular and humoral immune response. Our group has been developing a koalaChlamydia vaccine over the past 6 years using the recombinant major outer membrane protein (MOMP). While the koala-Chlamydia vaccine looks promising, it still needs to address some critical aspects. The present study aimed to extend the previous work by (a) evaluating a simpler vaccine to administer, preferably single dose vaccination, utilising a novel adjuvant formulation, (b) understanding the detailed mechanism that underpin humoral immunity in both naturally infected and vaccinated koalas, (c) determining the therapeutic Development of a chlamydial vaccine for koalas (Phascolarctos cinereus)Page ii and protective effects of the rMOMP vaccine strategy against the course of the infection in free-ranging koalas, and (d) understanding the role of the adjuvant on eliciting cellular and humoral responses in wild koalas.In koala, the current vaccine regime utilized recombinant C. pecorum specific major outer membrane protein (MOMP) as the vaccine antigen. This protein represents 60% of the chlamydial membrane structure and consists of T and B cell epitopes. While MOMP is the subunit component of the chlamydial outer membrane protein, a suitable adjuvant formulation could further enhance its immunogenicity. Several immunisation studies have used ISC (Immune stimulating complex) adjuvant and this has provided the best immune protection to date. One disadvantage of ISC is it requires multiple immunisations to be efficient. This requirement for several immunisations is not ideal as it could cause additional stress to the koala through repeated capture and handling processes. Therefore, to ove...