Induction of partial immunity in both males and females is sufficient to protect females against sexual transmission of Chlamydia

O’Meara, Connor P.; Armitage, Charles W.; Kollipara, Avinash; Andrew, Dean; Trim, Logan K; Plenderleith, Mark B.; Beagley, Kenneth W.

doi:10.1038/mi.2015.125

Cited by 39 publications

(45 citation statements)

References 30 publications

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“…In addition, the Th17 cells contribute to host protective immunity against bacterial pathogens and IL-17 secreted from Th17 cells was associated with protection against C . muridarum [52, 53]. Both 3MOMP and PmpG vaccines elicited a significantly increased expression of both IFN-γ and IL-17, post-vaccination.…”

Section: Discussionmentioning

confidence: 99%

Immunization of a wild koala population with a recombinant Chlamydia pecorum Major Outer Membrane Protein (MOMP) or Polymorphic Membrane Protein (PMP) based vaccine: New insights into immune response, protection and clearance

et al. 2017

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We assessed the effects of two different single-dose anti-Chlamydia pecorum (C. pecorum) vaccines (containing either Major Outer Membrane Protein (3MOMP) or Polymorphic Membrane Protein (Pmp) as antigens) on the immune response of a group of wild koalas. Both vaccines elicited a systemic humoral response as seen by the production of anti-chlamydial IgG antibodies in more than 90% of vaccinated koalas. A mucosal immune response was also observed, with an increase in Chlamydia-specific mucosal IgG and/or IgA antibodies in some koalas post-vaccination. Both vaccines elicited a cell-mediated immune response as measured by the production of the cytokines IFN-γ and IL-17 post-vaccination. To determine the level of protection provided by the vaccines under natural conditions we assessed C. pecorum infection loads and chlamydial disease status of all vaccinated koalas pre- and post-vaccination, compared to a non-vaccinated cohort from the same habitat. The MOMP vaccinated koalas that were infected on the day of vaccination showed significant clearance of their infection at 6 months post-vaccination. In contrast, the number of new infections in the PMP vaccine was similar to the control group, with some koalas progressing to disease. Genotyping of the ompA gene from the C. pecorum strains infecting the vaccinated animals, identified genetic variants of ompA-F genotype and a new genotype ompA-O. We found that those animals that were the least well protected became infected with strains of C. pecorum not covered by the vaccine. In conclusion, a single dose vaccine formulated with either recombinant PmpG or MOMP can elicit both cell-mediated and humoral (systemic and mucosal) immune responses, with the MOMP vaccine showing clearance of infection in all infected koalas. Although the capability of our vaccines to stimulate an adaptive response and be protective needs to be fully evaluated, this work illustrates the necessity to combine epitopes most relevant to a large panel of variable strains with an efficient adjuvant.

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Section: Discussionmentioning

confidence: 99%

Immunization of a wild koala population with a recombinant Chlamydia pecorum Major Outer Membrane Protein (MOMP) or Polymorphic Membrane Protein (PMP) based vaccine: New insights into immune response, protection and clearance

et al. 2017

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“…They showed that this vaccine can stimulate antigen specific systemic and mucosal antibody responses [80]. In a recent mouse study, these authors reported that rMOMP adjuvanted with ISC can reduce the infection burden and prevent subsequent oviduct pathology [81]. This study indicated that the vaccinated animals produced different cytokines and chemokines, specially, IFN-γ, TNF-α, at the genital mucosa.…”

Section: Discussionmentioning

confidence: 98%

“…One of the major findings of this study was that antibodies generated following vaccination might contribute towards immune protection through enhancing innate and adaptive responses [81].…”

Section: Discussionmentioning

confidence: 99%

“…The development of immunity at this time point would potentially reduce the transmission of chlamydial infection. Recent studies in a mouse model suggests the significant role of immunised male or female animals in subsequent disease transmission [81]. Additionally, few studies have focussed on the significant role of male koalas in disease transmission pose to critically address this gender issue in vaccine formulations.…”

Section: Future Directionsmentioning

confidence: 99%

“…In male koalas, infections are typically associated with conjunctivitis and genital infection can cause orchitis, epididymitis and prostatis [80]. Acute reproductive tract disease associated with severe inflammation in the mucosal epithelium reversibly (infertility) or irreversibly (sterility), in female koala, results in reproductive loss [81]. …”

Section: Types Of Koala-chlamydia Infectionmentioning

confidence: 99%

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Development of a chlamydial vaccine for koalas (Phascolarctos cinereus)

Khan¹

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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...

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Chlamydia Trachomatis Urogenital Infections

Armitage

Carey

Hickey

et al. 2018

Diagnostics to Pathogenomics of Sexually Transmitted Infections

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Quantitative evaluation of the cells involved in the immune system, such as lymphocytes, plasma cells, macrophages, dendritic cells, and epithelial cells, together with their products, including antibodies, cytokines, and humoral factors of innate immunity, convincingly revealed that the immune system associated with the mucosae is greater than its systemic counterpart (Russell et al. 2015a). This fact should not be surprising, as the development of the entire immune system during evolution and continuously in everyday life is driven by stimulation with commensal microbiota, antigens present in food and inhaled air, as well as pathogens throughout the enormous surface area of mucosal sites, which far exceeds the skin surface. The mucosal immune system comprises anatomically remote and physiologically distinct compartments that provide protection at various mucosal sites. Although the genital tract shares some common features with other mucosae, including the presence of humoral factors and cells of innate immunity, and the origin of cells involved in antibody production and T cell-mediated immunity, there are also many distinct features characteristic of the genital tract (Russell and Mestecky 2002, 2010; Mestecky et al. 2005). The spectrum of antigens including commensal or pathogenic microorganisms, and sperm is different from those at other mucosal sites. Furthermore, the primary physiological role of the genital tract is reproduction, which involves the acceptance of allogeneic sperm and semi-allogeneic offspring. This distinct physiological role influences the immune system of the genital tract with respect to the induction or suppression of immune responses, which must be considered in the development and application of vaccines against infectious agents of sexually transmitted diseases.

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Induction of partial immunity in both males and females is sufficient to protect females against sexual transmission of Chlamydia

Cited by 39 publications

References 30 publications

Immunization of a wild koala population with a recombinant Chlamydia pecorum Major Outer Membrane Protein (MOMP) or Polymorphic Membrane Protein (PMP) based vaccine: New insights into immune response, protection and clearance

Immunization of a wild koala population with a recombinant Chlamydia pecorum Major Outer Membrane Protein (MOMP) or Polymorphic Membrane Protein (PMP) based vaccine: New insights into immune response, protection and clearance

Development of a chlamydial vaccine for koalas (Phascolarctos cinereus)

Chlamydia Trachomatis Urogenital Infections

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