Recombinant antigens based on toxins A and B of Clostridium difficile that evoke a potent toxin-neutralising immune response

Maynard-Smith, Michael D.; Ahern, Helen; McGlashan, Joanna; Nugent, Philip; Ling, Roger; Denton, Harriet; Coxon, Ruth; Landon, J.; Roberts, April K.; Shone, Clifford C.

doi:10.1016/j.vaccine.2013.11.099

Cited by 16 publications

(16 citation statements)

References 37 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…In fact, the importance of the CPD in eliciting anti-TcdB neutralizing antibodies was also documented by a recent report, in which a TcdB fragment (TxB4) containing RBD and TMD only induced half the amount of anti-TcdB neutralizing antibodies when compared to another TcdB fragment (TxB5) comprised of the CPD in addition to the TMD and RBD. 45 …”

Section: Discussionmentioning

confidence: 99%

A chimeric protein comprising the glucosyltransferase and cysteine proteinase domains of toxin B and the receptor binding domain of toxin A induces protective immunity againstClostridium difficileinfection in mice and hamsters

Wang

Yan

Kim

et al. 2015

Human Vaccines & Immunotherapeutics

View full text Add to dashboard Cite

Section: Discussionmentioning

confidence: 99%

A chimeric protein comprising the glucosyltransferase and cysteine proteinase domains of toxin B and the receptor binding domain of toxin A induces protective immunity againstClostridium difficileinfection in mice and hamsters

Wang

Yan

Kim

et al. 2015

Human Vaccines & Immunotherapeutics

View full text Add to dashboard Cite

“…For example, the C‐terminal heavy chain domain of clostridial botulinum neurotoxin, a highly toxic protein that causes botulism, has been produced with BEVS and has demonstrated immunogenicity and challenge protection in mice [114, 115]. Recombinant toxin vaccines for other diseases such as Clostridium difficile could also be possible [116, 117].…”

Section: Conclusion and Future Opportunitiesmentioning

confidence: 99%

The baculovirus expression vector system: A commercial manufacturing platform for viral vaccines and gene therapy vectors

Felberbaum¹

2015

Biotechnology Journal

193

141

View full text Add to dashboard Cite

The baculovirus expression vector system (BEVS) platform has become an established manufacturing platform for the production of viral vaccines and gene therapy vectors. Nine BEVS-derived products have been approved - four for human use (Cervarix(®), Provenge(®), Glybera(®) and Flublok(®)) and five for veterinary use (Porcilis(®) Pesti, BAYOVAC CSF E2(®), Circumvent(®) PCV, Ingelvac CircoFLEX(®) and Porcilis(®) PCV). The BEVS platform offers many advantages, including manufacturing speed, flexible product design, inherent safety and scalability. This combination of features and product approvals has previously attracted interest from academic researchers, and more recently from industry leaders, to utilize BEVS to develop next generation vaccines, vectors for gene therapy, and other biopharmaceutical complex proteins. In this review, we explore the BEVS platform, detailing how it works, platform features and limitations and important considerations for manufacturing and regulatory approval. To underscore the growth in opportunities for BEVS-derived products, we discuss the latest product developments in the gene therapy and influenza vaccine fields that follow in the wake of the recent product approvals of Glybera(®) and Flublok(®), respectively. We anticipate that the utility of the platform will expand even further as new BEVS-derived products attain licensure. Finally, we touch on some of the areas where new BEVS-derived products are likely to emerge.

show abstract

“…In our previous study ( 25 , 26 ), and consistent with others ( 27 , 28 ), we indicated that the N-terminus of TcdB was able to elicit a protective antibody response. We ( 25 ) and others ( 29 ) also indicated that CPD could play important roles in maintaining the native structure or epitope conformation of GTD. In this study, we generated a new chimeric protein, Tcd169, by fusing GT, CPD, and RBD of TcdB and RBD of TcdA.…”

Section: Introductionmentioning

confidence: 72%

Novel Chimeric Protein Vaccines Against Clostridium difficile Infection

Wang

Cai

et al. 2018

Front. Immunol.

View full text Add to dashboard Cite

Clostridium difficile infection (CDI) is the leading cause of world-wide nosocomial acquired diarrhea in adults. Active vaccination is generally accepted as a logical and cost-effective approach to prevent CDI. In this paper, we have generated two novel chimeric proteins; one designated Tcd169, comprised of the glucosyltransferase domain (GT), the cysteine proteinase domain (CPD), and receptor binding domain (RBD) of TcdB, and the RBD of TcdA; the other designated Tcd169FI, which contains Salmonella typhimurium flagellin (sFliC) and Tcd169. Both proteins were expressed in and purified from Bacillus megaterium. Point mutations were made in the GT (W102A, D288N) and CPD (C698) of TcdB to ensure that Tcd169 and Tcd169FI were atoxic. Immunization with Tcd169 or Tcd169Fl induced protective immunity against TcdA/TcdB challenge through intraperitoneal injection, also provided mice full protection against infection with a hyper-virulent C. difficile strain (BI/NAP1/027). In addition, inclusion of sFlic in the fusion protein (Tcd169Fl) enhanced its protective immunity against toxin challenge, reduced C. difficile numbers in feces from Tcd169Fl-immunized mice infected C. difficile. Our data show that Tcd169 and Tcd169FI fusion proteins may represent alternative vaccine candidates against CDI.

show abstract

Recombinant antigens based on toxins A and B of Clostridium difficile that evoke a potent toxin-neutralising immune response

Cited by 16 publications

References 37 publications

A chimeric protein comprising the glucosyltransferase and cysteine proteinase domains of toxin B and the receptor binding domain of toxin A induces protective immunity againstClostridium difficileinfection in mice and hamsters

A chimeric protein comprising the glucosyltransferase and cysteine proteinase domains of toxin B and the receptor binding domain of toxin A induces protective immunity againstClostridium difficileinfection in mice and hamsters

The baculovirus expression vector system: A commercial manufacturing platform for viral vaccines and gene therapy vectors

Novel Chimeric Protein Vaccines Against Clostridium difficile Infection

Contact Info

Product

Resources

About