A re-evaluation of the role of B cells in protective immunity to Chlamydia infection

Li, Lin-Xi; McSorley, Stephen J.

doi:10.1016/j.imlet.2015.02.004

Cited by 42 publications

(32 citation statements)

References 78 publications

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“…B cell and antibody-mediated immunity against Chlamydia infection is not completely understood [38]. In 1997, Su et al demonstrated that B cell-deficient mice (μMT) cleared C. muridarium primary infections with normal kinetics of bacterial shedding from the genital tract but knockout mice were more susceptible to reinfection compared to wild type control mice [39].…”

Section: Immune Correlates Of Protective Immunity Against C Trachomatismentioning

confidence: 99%

Subunit vaccines for the prevention of mucosal infection with Chlamydia trachomatis

Karunakaran

Jiang

et al. 2016

Expert Review of Vaccines

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Chlamydia trachomatis is the most common preventable cause of tubal infertility in women. In high-income countries, despite public health control efforts, C. trachomatis case rates continue to rise. Most medium and low-income countries lack any Chlamydia control program; therefore, a vaccine is essential for the control of Chlamydia infections. A rationally designed Chlamydia vaccine requires understanding of the immunological correlates of protective immunity, pathological responses to this mucosal pathogen, identification of optimal vaccine antigens and selection of suitable adjuvant delivery systems that engender protective immunity. Fortunately, Chlamydia vaccinology is facilitated by genomic knowledge and by murine models that reproduce many of the features of human C. trachomatis infection. This article reviews recent progress in these areas with a focus on subunit vaccine development.

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Section: Immune Correlates Of Protective Immunity Against C Trachomatismentioning

confidence: 99%

Subunit vaccines for the prevention of mucosal infection with Chlamydia trachomatis

Karunakaran

Jiang

et al. 2016

Expert Review of Vaccines

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“…By comparison, the antibodies present in sera of naturally infected koalas with clinical disease, were found not to have any neutralisation ability. Although it has previously been thought that antibodies predominantly bind to the surface exposed epitopes to enable the neutralisation [86], we found that antibodies targeting apparently internal epitopes, such as those in the conserved/membrane anchored regions of MOMP, could also effectively neutralise infectivity. One possible explanation for this is that, recent studies have shown that antibodies can be taken up inside the epithelial cells through FcRn mediated transport and thereby neutralise virus [72] and intracellular bacteria, like Chlamydia [73].…”

Section: Discussioncontrasting

confidence: 52%

“…CD4+ T cells as well as CD8+ T cells are found at the infection site against C. trachomatis infection in human and mouse models [86,87]. Antigen presenting cells (APC) are able to phagocytose chlamydial EBs, degrade chlamydial components into peptides and present them in conjunction with MHC class II to the CD4+ T cells.…”

Section: Immunity Against Chlamydiamentioning

confidence: 99%

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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“…In addition, recent studies have highlighted anti-chlamydial immune responses via protective tissue resident memory T-cell subsets in vaccinated mice, 48 and B cells enhancing Ag-specific CD4 + T-cell priming upon infection. 56,57 In the context of a future Chlamydia vaccine and a possible role for CPAF, there is no consensus as to whether the desired outcome is a reduction in infectivity/transmission or a reduction in the clinically relevant chronic pathologies. Along with the reduction in bacterial shedding (around second week), we have previously demonstrated superior protection against upper reproductive pathologies with the rCPAF regimen, 11 including protection against infertility induced following repeated chlamydial challenge.…”

Section: Discussionmentioning

confidence: 99%

Chlamydial protease‐like activity factor mediated protection against C. trachomatis in guinea pigs

Wali

Gupta

et al. 2017

Immunol Cell Biol

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We have comprehensively demonstrated using the mouse model that intranasal immunization with recombinant chlamydial protease-like activity factor (rCPAF) leads to a significant reduction in bacterial burden, genital tract pathology and preserves fertility following intravaginal genital chlamydial challenge. In the present report, we evaluated the protective efficacy of rCPAF immunization in guinea pigs, a second animal model for genital chlamydial infection. Using a vaccination strategy similar to the mouse model, we intranasally immunized female guinea pigs with rCPAF plus CpG deoxynucleotides (CpG; as an adjuvant), and challenged intravaginally with C. trachomatis serovar D (CT-D). Immunization with rCPAF/CpG significantly reduced vaginal CT-D shedding and induced resolution of infection by day 24, compared to day 33 in CpG alone treated and challenged animals. Immunization induced robust anti-rCPAF serum IgG 2 weeks following the last immunization, and was sustained at a high level 4 weeks post challenge. Upregulation of antigen specific IFN-γ gene expression was observed in rCPAF/CpG vaccinated splenocytes. Importantly, a significant reduction in inflammation in the genital tissue in rCPAF/CpG-immunized guinea pigs compared to CpG-immunized animals was observed. Taken together, this study provides evidence of the protective efficacy of rCPAF as a vaccine candidate in a second animal model of genital chlamydial infection.

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A re-evaluation of the role of B cells in protective immunity to Chlamydia infection

Cited by 42 publications

References 78 publications

Subunit vaccines for the prevention of mucosal infection with Chlamydia trachomatis

Subunit vaccines for the prevention of mucosal infection with Chlamydia trachomatis

Development of a chlamydial vaccine for koalas (Phascolarctos cinereus)

Chlamydial protease‐like activity factor mediated protection against C. trachomatis in guinea pigs

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