Mimicking Native Display of CD0873 on Liposomes Augments Its Potency as an Oral Vaccine against Clostridioides difficile

Karyal, Cansu; Palazi, Panayiota; Hughes, Jaime; Griffiths, Rhys C.; Persaud, Ruby; Tighe, Patrick J.; Mitchell, Nick; Griffin, Ruth

doi:10.3390/vaccines9121453

Cited by 7 publications

(20 citation statements)

References 50 publications

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“…To further test for the presence of antigen-specific IgG in vaccinated sera, 96-well plates were coated in recombinant protein antigen, either CD0873 or TcdB-RBD as previously described [ 25 , 47 ]. After blocking, sera diluted 1:10 were added and bound antibody detected using goat anti-hamster IgG Biotin-labelled secondary antibody and Streptavidin-HRP.…”

Section: Resultsmentioning

confidence: 99%

“…NTCD T7 was chosen, as this strain was previously characterised for its biotherapeutic properties against CDI in the hamster model [ 45 , 46 ]. The colonisation factor, CD0873, was chosen as we showed that it induces colonisation blocking antibodies in hamsters when given as recombinant protein orally [ 25 , 47 ]. The receptor binding domain (RBD) of TcdB was chosen, as it is known to be immunogenic and to confer full protection in mice [ 48 ].…”

Section: Introductionmentioning

confidence: 99%

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Towards Development of a Non-Toxigenic Clostridioides difficile Oral Spore Vaccine against Toxigenic C. difficile

et al. 2022

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Clostridioides difficile is an opportunistic gut pathogen which causes severe colitis, leading to significant morbidity and mortality due to its toxins, TcdA and TcdB. Two intra-muscular toxoid vaccines entered Phase III trials and strongly induced toxin-neutralising antibodies systemically but failed to provide local protection in the colon from primary C. difficile infection (CDI). Alternatively, by immunising orally, the ileum (main immune inductive site) can be directly targeted to confer protection in the large intestine. The gut commensal, non-toxigenic C. difficile (NTCD) was previously tested in animal models as an oral vaccine for natural delivery of an engineered toxin chimera to the small intestine and successfully induced toxin-neutralising antibodies. We investigated whether NTCD could be further exploited to induce antibodies that block the adherence of C. difficile to epithelial cells to target the first stage of pathogenesis. In NTCD strain T7, the colonisation factor, CD0873, and a domain of TcdB were overexpressed. Following oral immunisation of hamsters with spores of recombinant strain, T7-0873 or T7-TcdB, intestinal and systemic responses were investigated. Vaccination with T7-0873 successfully induced intestinal antibodies that significantly reduced adhesion of toxigenic C. difficile to Caco-2 cells, and these responses were mirrored in sera. Additional engineering of NTCD is now warranted to further develop this vaccine.

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Section: Resultsmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Towards Development of a Non-Toxigenic Clostridioides difficile Oral Spore Vaccine against Toxigenic C. difficile

et al. 2022

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“…Previous studies have demonstrated that outer membrane vesicles (OMVs) from E. coli encapsulated into Zein Nanoparticles coated with a Gantrez ® AN–Mannosamine Polymer Conjugate elicited high levels of IgG antibodies, while oral administration of the outer membrane protein alone did not elicit an antibody response ( 43 ). In contrast, displaying CD0873 on liposomes without encapsulation elicited significantly different IgG and IgA titers from the control group after three oral immunizations ( 44 ). Oral exposure to stx+ eae+ intimin-positive E. coli O157: H7 as an oral vaccine twice weekly for 6 weeks would increase resistance of cattle to colonization by wild-type E. coli O157: H7 following challenge ( 45 ).…”

Section: Discussionmentioning

confidence: 99%

Comparative study of subcutaneous, intramuscular, and oral administration of bovine pathogenic Escherichia coli bacterial ghost vaccine in mice

Lei

Zheng

et al. 2022

Front. Immunol.

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Escherichia coli is one of the most common bacterial pathogens in cattle. Prophylactic vaccines are considered promising strategies with the potential to reduce the incidence of colibacillosis. Some studies suggested that bacterial ghosts may serve as a novel approach for preventing bacterial infections. However, the roles of administration route on vaccine immunogenicity and efficacy have not been investigated. In this study, the efficacy of vaccination via different immune routes in generating humoral and cellular immune response was compared through subcutaneous (SC), intramuscular (IM), and oral (O) administration in female BALB/c mice with bacterial ghosts prepared using wild type Escherichia coli isolates CE9, while phosphate buffer saline (PBS) and inactivated vaccines containing aluminum adjuvants (Killed) were used as control. Our results showed that the plasmid pBV220-E-aa-SNA containing E. coli was efficiently cleaved at 42°C with 94.8% positive ratio as assessed by colony counts. Transmission electron microscopy (TEM) confirmed bacteria retained intact surface structure while devoid of cytoplasmic component. We found that total IgG titers in killed, IM and SC groups showed significant increase on 7, 14, 21 and 28 days post-immunization. The IgA level of the IM group was higher than that of all other groups on the 28th day. Meanwhile, four experimental groups showed a significant difference in IgA levels compared with PBS control. In the IM group, an increase in the relative percentages of CD3+CD4+ T cells was accompanied by an increase in the relative percentages of splenic CD3+CD8+ T cells. In comparison with the inactivated vaccine, intramuscular CE9 ghosts immunization elicited higher levels of IL-1β, IL-2, IL-6 and IL-12. Subcutaneous and intramuscular immunizations were significantly associated with improved survival in comparison with oral route, traditional vaccine and the control. Pathologic assessment revealed that less severe tissue damage and inflammation were found in lung, kidney, and intestine of IM group compared with other groups. The results above demonstrate that immunization of Escherichia coli CE9 ghosts via intramuscular injection elicits a more robust antigen-specific immune response in mice to prevent the Escherichia coli infection.

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“…This strong immune response to CD0873 offered 80% protection from death in the study [ 121 ]. A subsequent study by Karyal et al demonstrated the use of liposomes to more effectively deliver the CD0873 antigen [ 122 ]. Not only does this appear to be the first use of a liposome delivery system for CDI vaccination, but this delivery strategy produced a more effective neutralizing antibody response as measured by greater inhibition of C. difficile adherence by vaccine-induced antibodies [ 122 ].…”

Section: Surface-antigen Mucosal Vaccinementioning

confidence: 99%

“…A subsequent study by Karyal et al demonstrated the use of liposomes to more effectively deliver the CD0873 antigen [ 122 ]. Not only does this appear to be the first use of a liposome delivery system for CDI vaccination, but this delivery strategy produced a more effective neutralizing antibody response as measured by greater inhibition of C. difficile adherence by vaccine-induced antibodies [ 122 ]. The authors indicated that the increased effectiveness of liposome-displayed CD0873 could be due to reduced protein aggregation, greater uptake of the vaccine by M cells, and interactions with macrophages due to the specific liposome composition.…”

Section: Surface-antigen Mucosal Vaccinementioning

confidence: 99%

Mucosal Vaccination Strategies against Clostridioides difficile Infection

2023

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Clostridioides difficile infection (CDI) presents a major public health threat by causing frequently recurrent, life-threatening cases of diarrhea and intestinal inflammation. The ability of C. difficile to express antibiotic resistance and to form long-lasting spores makes the pathogen particularly challenging to eradicate from healthcare settings, raising the need for preventative measures to curb the spread of CDI. Since C. difficile utilizes the fecal–oral route of transmission, a mucosal vaccine could be a particularly promising strategy by generating strong IgA and IgG responses that prevent colonization and disease. This mini-review summarizes the progress toward mucosal vaccines against C. difficile toxins, cell–surface components, and spore proteins. By assessing the strengths and weaknesses of particular antigens, as well as methods for delivering these antigens to mucosal sites, we hope to guide future research toward an effective mucosal vaccine against CDI.

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Mimicking Native Display of CD0873 on Liposomes Augments Its Potency as an Oral Vaccine against Clostridioides difficile

Cited by 7 publications

References 50 publications

Towards Development of a Non-Toxigenic Clostridioides difficile Oral Spore Vaccine against Toxigenic C. difficile

Towards Development of a Non-Toxigenic Clostridioides difficile Oral Spore Vaccine against Toxigenic C. difficile

Comparative study of subcutaneous, intramuscular, and oral administration of bovine pathogenic Escherichia coli bacterial ghost vaccine in mice

Mucosal Vaccination Strategies against Clostridioides difficile Infection

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