Vaccination of koalas during antibiotic treatment for Chlamydia-induced cystitis induces an improved antibody response to Chlamydia pecorum

Abstract

Chlamydia infection and disease are endemic in free-ranging koalas. Antibiotics remain the front line treatment for Chlamydia in koalas, despite their rates of treatment failure and adverse gut dysbiosis outcomes. A Chlamydia vaccine for koalas has shown promise for replacing antibiotic treatment in mild ocular Chlamydia disease. in more severe disease presentations that require antibiotic intervention, the effect of vaccinating during antibiotic use is not currently known. This study investigated whether a productive immune response could be induced by vaccinating koalas during antibiotic treatment for Chlamydia-induced cystitis. plasma igG antibody levels against the C. pecorum major outer membrane protein (MoMp) dropped during antibiotic treatment in both vaccinated and unvaccinated koalas. post-treatment, igG levels recovered. the igG antibodies from naturally-infected, vaccinated koalas recognised a greater proportion of the MoMp protein compared to their naturally-infected, unvaccinated counterparts. furthermore, peripheral blood mononuclear cell gene expression revealed an up-regulation in genes related to neutrophil degranulation in vaccinated koalas during the first month post-vaccination. These findings show that vaccination of koalas while they are being treated with antibiotics for cystitis can result in the generation of a productive immune response, in the form of increased and expanded igG production and host response through neutrophil degranulation.

The Koala Immune Response to Chlamydial Infection and Vaccine Development—Advancing Our Immunological Understanding

“…Koala-specific reagents for experimentation have also been limited, given the non-model organism status of this marsupial. However, despite these limitations, chlamydial vaccine development for koalas has progressed over the last decade to generate research vaccine formulations with very promising efficacies [ 13 , 14 , 15 ]. Research has also highlighted many similarities in immune responses to Chlamydia infection between hosts, allowing for knowledge from one host to guide research in others.…”

“…Interestingly, despite the well-recognised importance of IFN-γ, there have also been smaller studies where positive vaccine outcomes were achieved and increases in IFN-γ levels could not be detected in koalas post-vaccination [ 14 , 15 ]. Although sample timing can always be a factor in detecting cytokine expression, the genetics of C. pecorum may also inform on the variable IFN-γ detection.…”

“…In every chlamydial vaccine trial in koalas where antibodies were measured, there has been a detectable increase in systemic IgG to C. pecorum post-vaccination, regardless of the vaccine formulation tested [ 5 ]. Characterisation of these systemic C. pecorum IgG antibodies has found that, (a) diverse MOMP genotypes, including genotypes not included as antigen in the vaccine, could be recognised [ 58 ], (b) vaccination induced a greater epitope recognition compared to natural infection (including to conserved regions of MOMP) [ 15 , 59 , 60 ] and that (c) vaccination increased the neutralisation effect of the antibodies generated [ 60 ]. Given the fact that C. pecorum is currently recognised to have 15 MOMP genotypes associated with koalas [ 4 ], achieving antibody responses to multiple MOMP genotype has offered promise that vaccination may induce heterologous protection.…”

“…This has led to increased levels of IL-17 expression being strongly associated with decreases in urogenital chlamydial load and less chlamydial disease in these trials [ 54 ]. Looking globally, total transcriptome profiling of koala PBMCs one-month post-vaccination has further expanded links to inflammation-related pathways, with significant up-regulation of 26 genes involved in neutrophil degranulation detected [ 15 ]. Collectively, these results continue to support the multi-faceted anti-chlamydial immune response observed in other hosts, with aspects of the Th17 response having a place in vaccination responses in koalas ( Figure 3 ).…”

Is Chlamydia to Blame for Koala Reproductive Cysts?

“…Chlamydia infections in the koala are treated with antibiotics for extended periods of time (up to 45 days) resulting in complete bacterial clearance [ 9 , 13 ]. Unfortunately, some wild koalas develop chronic, advanced disease before being found and brought to wildlife hospitals, furthermore, antibiotic treatment failure occurs, resulting in disease progression and eventual death [ 14 ]. Reproductive tract disease can progress in female koalas and result in reproductive cyst development and presumed infertility [ 9 ].…”