A Prototype Recombinant-Protein Based Chlamydia pecorum Vaccine Results in Reduced Chlamydial Burden and Less Clinical Disease in Free-Ranging Koalas (Phascolarctos cinereus)

Waugh, Courtney; Khan, Shahneaz Ali; Carver, Scott; Hanger, Jon; Loader, Joanne; Polkinghorne, Adam; Beagley, Kenneth W.; Timms, Peter

doi:10.1371/journal.pone.0146934

Cited by 45 publications

(81 citation statements)

References 15 publications

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“…Koalas in this population have been captured and radio collared in order to be able to undergo veterinary assessments and sampling at 6 monthly intervals 41 , thereby providing a large database of animals for which we had longitudinal datum for each animal. Criteria for inclusion into the study were animals (male and female) of breeding age (>1 year), age was estimated from tooth wear imand growth 44, 45 .…”

Section: Methodsmentioning

confidence: 99%

Infection with koala retrovirus subgroup B (KoRV-B), but not KoRV-A, is associated with chlamydial disease in free-ranging koalas (Phascolarctos cinereus)

Waugh

Hanger

Loader

et al. 2017

Sci Rep

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117

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The virulence of chlamydial infection in wild koalas is highly variable between individuals. Some koalas can be infected (PCR positive) with Chlamydia for long periods but remain asymptomatic, whereas others develop clinical disease. Chlamydia in the koala has traditionally been studied without regard to coinfection with other pathogens, although koalas are usually subject to infection with koala retrovirus (KoRV). Retroviruses can be immunosuppressive, and there is evidence of an immunosuppressive effect of KoRV in vitro. Originally thought to be a single endogenous strain, a new, potentially more virulent exogenous variant (KoRV-B) was recently reported. We hypothesized that KoRV-B might significantly alter chlamydial disease outcomes in koalas, presumably via immunosuppression. By studying sub-groups of Chlamydia and KoRV infected koalas in the wild, we found that neither total KoRV load (either viraemia or proviral copies per genome), nor chlamydial infection level or strain type, was significantly associated with chlamydial disease risk. However, PCR positivity with KoRV-B was significantly associated with chlamydial disease in koalas (p = 0.02961). This represents an example of a recently evolved virus variant that may be predisposing its host (the koala) to overt clinical disease when co-infected with an otherwise asymptomatic bacterial pathogen (Chlamydia).

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Section: Methodsmentioning

confidence: 99%

Infection with koala retrovirus subgroup B (KoRV-B), but not KoRV-A, is associated with chlamydial disease in free-ranging koalas (Phascolarctos cinereus)

Waugh

Hanger

Loader

et al. 2017

Sci Rep

Self Cite

117

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“…Samples were collected from ocular (both sexes), urogenital tract (UGT) of females and penile site of males, as described previously 40 . In total 544 samples (ocular and/or urogenital) from 232 animals were included in the study with sampling at 1 or 2 time points (Supplementary Table S5).…”

Section: Methodsmentioning

confidence: 99%

Microbiota composition of the koala (Phascolarctos cinereus) ocular and urogenital sites, and their association with Chlamydia infection and disease

Vidgen

Hanger

2017

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Disease caused by Chlamydia pecorum is characterised by ocular and urogenital infections that can lead to blindness and infertility in koalas. However, koalas that are infected with C. pecorum do not always progress to disease. In other host systems, the influence of the microbiota has been implicated in either accelerating or preventing infections progressing to disease. This study investigates the contribution of koala urogenital and ocular microbiota to Chlamydia infection and disease in a free ranging koala population. Using univariate and multivariate analysis, it was found that reproductive status in females and sexual maturation in males, were defining features in the koala urogenital microbiota. Changes in the urogenital microbiota of koalas is correlated with infection by the common pathogen, C. pecorum. The correlation of microbiota composition and C. pecorum infection is suggestive of members of the microbiota being involved in the acceleration or prevention of infections progressing to disease. The analysis also suggests that multiple microbes are likely to be associated with this process of disease progression, rather than a single organism. While other Chlamydia-like organisms were also detected, they are unlikely to contribute to chlamydial disease as they are rare members of the urogenital and ocular microbiota communities.

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“…Koala bears which are being devastated by chlamydial infections would also benefit from a genus-wide vaccine. (Waugh et al, 2016)…”

Section: Introductionmentioning

confidence: 99%

Dendrimer-conjugated peptide vaccine enhances clearance of Chlamydia trachomatis genital infection

Ganda

Zhong

Hali

et al. 2017

International Journal of Pharmaceutics

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Peptide-based vaccines have emerged in recent years as promising candidates in the prevention of infectious diseases. However, there are many challenges to maintaining in vivo peptide stability and enhancement of peptide immunogenicity to generate protective immunity which enhances clearance of infections. Here, a dendrimer-based carrier system is proposed for peptide-based vaccine delivery, and shows its anti-microbial feasibility in a mouse model of Chlamydia trachomatis. Chlamydiae are the most prevalent sexually transmitted bacteria worldwide, and also the causal agent of trachoma, the leading cause of preventable infectious blindness. In spite of the prevalence of this infectious agent and the many previous vaccine-related studies, there is no vaccine commercially available. The carrier system proposed consists of generation 4, hydroxyl-terminated, polyamidoamine (PAMAM) dendrimers (G4OH), to which a peptide mimic of a chlamydial glycolipid antigen—Peptide 4 (Pep4, AFPQFRSATLLL) was conjugated through an ester bond. The ester bond between G4OH and Pep4 is expected to break down mainly in the intracellular environment for antigen presentation. Pep4 conjugated to dendrimer induced Chlamydia-specific serum antibodies after subcutaneous immunizations. Further, this new vaccine formulation significantly protected immunized animals from vaginal challenge with infectious Chlamydia trachomatis, and it reduced infectious loads and tissue (genital tract) damage. Pep4 conjugated to G4OH or only mixed with peptide provided enhanced protection compared to Pep4 and adjuvant (i.e. alum), suggesting a potential adjuvant effect of the PAMAM dendrimer. Combined, these results demonstrate that hydroxyl-terminated PAMAM dendrimer is a promising polymeric nanocarrier platform for the delivery of peptide vaccines and this approach has potential to be expanded to other infectious intracellular bacteria and viruses of public health significance.

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A Prototype Recombinant-Protein Based Chlamydia pecorum Vaccine Results in Reduced Chlamydial Burden and Less Clinical Disease in Free-Ranging Koalas (Phascolarctos cinereus)

Cited by 45 publications

References 15 publications

Infection with koala retrovirus subgroup B (KoRV-B), but not KoRV-A, is associated with chlamydial disease in free-ranging koalas (Phascolarctos cinereus)

Infection with koala retrovirus subgroup B (KoRV-B), but not KoRV-A, is associated with chlamydial disease in free-ranging koalas (Phascolarctos cinereus)

Microbiota composition of the koala (Phascolarctos cinereus) ocular and urogenital sites, and their association with Chlamydia infection and disease

Dendrimer-conjugated peptide vaccine enhances clearance of Chlamydia trachomatis genital infection

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