Glycoengineered Outer Membrane Vesicles: A Novel Platform for Bacterial Vaccines

Price, Nancy L.; Goyette-Desjardins, Guillaume; Nothaft, Harald; Valguarnera, Ezequiel; Szymanski, Christine M.; Segura, Mariela; Feldman, Mario F.

doi:10.1038/srep24931

Cited by 106 publications

(95 citation statements)

References 48 publications

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“…We previously demonstrated that the C. jejuni N-glycan is an effective antigen in various vaccine formulations, including glycoprotein conjugates, E. coli surface expression carriers, and outer membrane vesicles (36,42). To date, the live E. coli vaccine comprised of the N-glycan attached to the LOS core demonstrated the greatest success in significantly reducing C. jejuni colonization in leghorn chicken challenge studies (36).…”

Section: Discussionmentioning

confidence: 99%

Coadministration of the Campylobacter jejuni N-Glycan-Based Vaccine with Probiotics Improves Vaccine Performance in Broiler Chickens

Nothaft

Pérez-Muñoz

Gouveia

et al. 2017

Appl Environ Microbiol

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Source attribution studies report that the consumption of contaminated poultry is the primary source for acquiring human campylobacteriosis. Oral administration of an engineered Escherichia coli strain expressing the Campylobacter jejuni N-glycan reduces bacterial colonization in specific-pathogen-free leghorn chickens, but only a fraction of birds respond to vaccination. Optimization of the vaccine for commercial broiler chickens has great potential to prevent the entry of the pathogen into the food chain. Here, we tested the same vaccination approach in broiler chickens and observed similar efficacies in pathogen load reduction, stimulation of the host IgY response, the lack of C. jejuni resistance development, uniformity in microbial gut composition, and the bimodal response to treatment. Gut microbiota analysis of leghorn and broiler vaccine responders identified one member of Clostridiales cluster XIVa, Anaerosporobacter mobilis, that was significantly more abundant in responder birds. In broiler chickens, coadministration of the live vaccine with A. mobilis or Lactobacillus reuteri, a commonly used probiotic, resulted in increased vaccine efficacy, antibody responses, and weight gain. To investigate whether the respondernonresponder effect was due to the selection of a C. jejuni "supercolonizer mutant" with altered phase-variable genes, we analyzed all poly(G)-containing loci of the input strain compared to nonresponder colony isolates and found no evidence of phase state selection. However, untargeted nuclear magnetic resonance (NMR)-based metabolomics identified a potential biomarker negatively correlated with C. jejuni colonization levels that is possibly linked to increased microbial diversity in this subgroup. The comprehensive methods used to examine the bimodality of the vaccine response provide several opportunities to improve the C. jejuni vaccine and the efficacy of any vaccination strategy.IMPORTANCE Campylobacter jejuni is a common cause of human diarrheal disease worldwide and is listed by the World Health Organization as a high-priority pathogen. C. jejuni infection typically occurs through the ingestion of contaminated chicken meat, so many efforts are targeted at reducing C. jejuni levels at the source. We previously developed a vaccine that reduces C. jejuni levels in egg-laying chickens. In this study, we improved vaccine performance in meat birds by supplementing the vaccine with probiotics. In addition, we demonstrated that C. jejuni colonization levels in chickens are negatively correlated with the abundance of clostridia, another group of common gut microbes. We describe new methods for vaccine op-

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Section: Discussionmentioning

confidence: 99%

Coadministration of the Campylobacter jejuni N-Glycan-Based Vaccine with Probiotics Improves Vaccine Performance in Broiler Chickens

Nothaft

Pérez-Muñoz

Gouveia

et al. 2017

Appl Environ Microbiol

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“…In this regard, rigorous evaluation of prebiotic and probiotic outcomes (149) and establishment of realistic production benchmarks are mandatory before there will be further adoption by industry. Alternatively, the engineering of intestinal microorganisms, such as chimeric live vaccines (150,151), CRISPR-based genome editing (152), and synthetic biology of secondary metabolism (153), holds vast potential and may ultimately transform how food is produced in the future.…”

Section: Conclusion and Future Perspectivesmentioning

confidence: 99%

Polysaccharide Utilization Loci: Fueling Microbial Communities

et al. 2017

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The complex carbohydrates of terrestrial and marine biomass represent a rich nutrient source for free-living and mutualistic microbes alike. The enzymatic saccharification of these diverse substrates is of critical importance for fueling a variety of complex microbial communities, including marine, soil, ruminant, and monogastric microbiota. Consequently, highly specific carbohydrate-active enzymes, recognition proteins, and transporters are enriched in the genomes of certain species and are of critical importance in competitive environments. In Bacteroidetes bacteria, these systems are organized as polysaccharide utilization loci (PULs), which are strictly regulated, colocalized gene clusters that encode enzyme and protein ensembles required for the saccharification of complex carbohydrates. This review provides historical perspectives and summarizes key findings in the study of these systems, highlighting a critical shift from sequence-based PUL discovery to systems-based analyses combining reverse genetics, biochemistry, enzymology, and structural biology to precisely illuminate the molecular mechanisms underpinning PUL function. The ecological implications of dynamic PUL deployment by key species in the human gastrointestinal tract are explored, as well as the wider distribution of these systems in other gut, terrestrial, and marine environments.

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“…Outer membrane vesicles (OMVs) are protrusions of the outer membrane of gram‐negative bacteria, which have become popular as a vaccine delivery platform over the past few years. In their recent work, Price et al . described non‐pathogenic E. coli strains engineered to express surface glycans from other bacterial pathogens on their membranes.…”

Section: Multivalency In Immune Cell Modulationmentioning

confidence: 99%

Designing Multivalent Ligands to Control Biological Interactions: From Vaccines and Cellular Effectors to Targeted Drug Delivery

Arsiwala

Castro

Frey

et al. 2019

Chemistry An Asian Journal

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Multivalent interactions in which multiple ligands on one object bind to multiple receptors on another are commonly found in natural biological systems. In addition, these interactions can lead to increased strength and selectivity when compared to the corresponding monovalent interaction. These attributes have also guided the design of synthetic multivalent ligands to control biological interactions. This review will highlight the recent literature describing the use of multivalent ligand display in the design of vaccines, immunomodulators, cell signaling effectors, and vehicles for targeted drug delivery.

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Glycoengineered Outer Membrane Vesicles: A Novel Platform for Bacterial Vaccines

Cited by 106 publications

References 48 publications

Coadministration of the Campylobacter jejuni N-Glycan-Based Vaccine with Probiotics Improves Vaccine Performance in Broiler Chickens

Coadministration of the Campylobacter jejuni N-Glycan-Based Vaccine with Probiotics Improves Vaccine Performance in Broiler Chickens

Polysaccharide Utilization Loci: Fueling Microbial Communities

Designing Multivalent Ligands to Control Biological Interactions: From Vaccines and Cellular Effectors to Targeted Drug Delivery

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