<i>Chlamydia trachomatis</i>vaccines for genital infections: where are we and how far is there to go?

Maza, Luis M. de la; Darville, Toni; Pal, Sukumar

doi:10.1080/14760584.2021.1899817

Cited by 46 publications

(52 citation statements)

References 181 publications

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“…Along similar lines, Chlamydia major outer membrane protein (MOMP) is a β -barrel integral membrane protein (IMP) that accounts for ~60% of the mass of the outer membrane of Chlamydia spp. (46,47) and is highly antigenic (48), making it an attractive subunit vaccine candidate (49). However, expression of MOMP in the E. coli cytoplasm results in aggregation and the formation of inclusion bodies (50,51) while expression in the E. coli outer membrane results in significant cell toxicity (50,52,53).…”

Section: Decoration Of Omv Surfaces With Structurally Diverse Antigensmentioning

confidence: 99%

“…Encouraged by the immunostimulation observed for SNARE-OMVs remodeled with the model GFP antigen, we next investigated the humoral immune response to SNARE-OMVs that were decorated with Cm-MOMP, a validated subunit vaccine candidate (49,51). Prior to immunization, we first tested the antigenicity of our Sx-Cm-MOMP construct (Fig.…”

Section: Immunogenicity Of Snare-omvs Loaded With Validated Cm-momp Antigenmentioning

confidence: 99%

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A modular platform for on-demand vaccine self-assembly enabled by decoration of bacterial outer membrane vesicles with biotinylated antigens

Weyant

Liao²,

Jesus

et al. 2021

Preprint

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Engineered outer membrane vesicles (OMVs) derived from laboratory strains of bacteria are a promising technology for the creation of non-infectious, nanoparticle vaccines against diverse pathogens. As mimics of the bacterial cell surface, OMVs offer a molecularly-defined architecture for programming repetitive, high-density display of heterologous antigens in conformations that elicit strong B and T cell immune responses. However, antigen display on the surface of OMVs can be difficult to control and highly variable due to bottlenecks in protein expression and localization to the outer membrane of the host cell, especially for bulky and/or complex antigens. To address this shortcoming, we created a universal approach called AddVax (avidin-based dock-and-display for vaccine antigen cross (x)-linking) whereby virtually any antigen that is amenable to biotinylation can be linked to the exterior of OMVs whose surfaces are remodeled with multiple copies of a synthetic antigen receptor (SNARE) comprised of an outer membrane scaffold protein fused to a member of the avidin family. We show that SNARE-OMVs can be readily decorated with a molecularly diverse array of biotinylated subunit antigens, including globular and membrane proteins, glycans and glycoconjugates, haptens, lipids, and short peptides. When the resulting OMV formulations were injected in wild-type BALB/c mice, strong antigen-specific antibody responses were observed that depended on the physical coupling between the antigen and SNARE-OMV delivery vehicle. Overall, these results demonstrate AddVax as a modular platform for rapid self-assembly of antigen-studded OMVs with the potential to accelerate vaccine generation, respond rapidly to pathogen threats in humans and animals, and simplify vaccine stockpiling.

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Section: Decoration Of Omv Surfaces With Structurally Diverse Antigensmentioning

confidence: 99%

Section: Immunogenicity Of Snare-omvs Loaded With Validated Cm-momp Antigenmentioning

confidence: 99%

A modular platform for on-demand vaccine self-assembly enabled by decoration of bacterial outer membrane vesicles with biotinylated antigens

Weyant

Liao²,

Jesus

et al. 2021

Preprint

Self Cite

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“…After endocytosis, the EBs transform into reticulate bodies (RBs) of low metabolic activity. The RBs then replicate and re-differentiate into the EBs that are released to infect neighboring cells [3,4].…”

Section: Introductionmentioning

confidence: 99%

Overexpression of the Bam Complex Improves the Production of Chlamydia trachomatis MOMP in the E. coli Outer Membrane

Huynh

Jong

Koningstein

et al. 2022

IJMS

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A licensed Chlamydia trachomatis (Ct) vaccine is not yet available. Recombinant Chlamydia trachomatis major outer membrane protein (Ct-MOMP), the most abundant constituent of the chlamydial outer membrane complex, is considered the most attractive candidate for subunit-based vaccine formulations. Unfortunately, Ct-MOMP is difficult to express in its native structure in the E. coli outer membrane (OM). Here, by co-expression of the Bam complex, we improved the expression and localization of recombinant Ct-MOMP in the E. coli OM. Under these conditions, recombinant Ct-MOMP appeared to assemble into a β-barrel conformation and express domains at the cell surface indicative of correct folding. The data indicate that limited availability of the Bam complex can be a bottleneck for the production of heterologous OM vaccine antigens, information that is also relevant for strategies aimed at producing recombinant OMV-based vaccines.

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“…Left untreated, it can spread to the upper genital tract, inducing chronic inflammation and ultimately pelvic inflammatory disease and infertility ( Murray and McKay, 2021 ). Despite the availability of antibiotic treatments, an effective vaccine is needed to control the infection rate ( de la Maza et al, 2017 , 2021 ). All species of Chlamydiae share a unique developmental cycle.…”

Section: Introductionmentioning

confidence: 99%

“…Moreover, PmpD is shown to be involved in immune response modulation ( Chu et al, 2020 ). For all these reasons, Pmps are considered valuable candidates for the development of a vaccine ( Müller et al, 2017 ; Pal et al, 2017 ; de la Maza et al, 2021 ), therefore studying their biochemical and biological properties is of main interest. Proteome studies of C. trachomatis EBs and RBs revealed that most Pmps are processed during infection, generating fragments of different length and with different densities of the two repeat motifs ( Saka et al, 2011 ).…”

Section: Introductionmentioning

confidence: 99%

Chlamydia trachomatis Polymorphic Membrane Proteins (Pmps) Form Functional Homomeric and Heteromeric Oligomers

Favaroni

Hegemann

2021

Front. Microbiol.

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Chlamydiae are Gram-negative, obligate intracellular bacteria, which infect animals and humans. Adhesion to host cells, the first step in the infection process, is mediated by polymorphic membrane proteins (Pmps). Pmps constitute the largest chlamydial protein family, with 9 members (subdivided into six subtypes) in C. trachomatis and 21 in C. pneumoniae, and are characterized by the presence of multiple copies of GGA(I,L,V) and FxxN motifs. Motif-rich fragments of all nine C. trachomatis Pmps act as adhesins and are essential for infection. As autotransporters, most Pmp proteins are secreted through their β-barrel domain and localize on the surface of the chlamydial cell, where most of them are proteolytically processed. Classical autotransporters are monomeric proteins, which can function as toxins, proteases, lipases and monoadhesive adhesins. Here we show that selected recombinant C. trachomatis Pmp fragments form functional adhesion-competent multimers. They assemble into homomeric and heteromeric filaments, as revealed by non-denaturing gel electrophoresis, size-exclusion chromatography and electron microscopy. Heteromeric filaments reach 2 μm in length, significantly longer than homomeric structures. Filament formation was independent of the number of motifs present in the fragment(s) concerned and their relative affinity for host cells. Our functional studies demonstrated that only adhesion-competent oligomers were able to block a subsequent infection. Pre-loading of infectious chlamydial cells with adhesion-competent Pmp oligomers maintained the subsequent infection, while adhesion-incompetent structures reduced infectivity, presumably by blocking the function of endogenous Pmps. The very large number of possible heteromeric and homomeric Pmp complexes represents a novel mechanism to ensure stable adhesion and possibly host cell immune escape.

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Chlamydia trachomatisvaccines for genital infections: where are we and how far is there to go?

Cited by 46 publications

References 181 publications

A modular platform for on-demand vaccine self-assembly enabled by decoration of bacterial outer membrane vesicles with biotinylated antigens

A modular platform for on-demand vaccine self-assembly enabled by decoration of bacterial outer membrane vesicles with biotinylated antigens

Overexpression of the Bam Complex Improves the Production of Chlamydia trachomatis MOMP in the E. coli Outer Membrane

Chlamydia trachomatis Polymorphic Membrane Proteins (Pmps) Form Functional Homomeric and Heteromeric Oligomers

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