Safety, immunogenicity, and efficacy of a Clostridioides difficile toxoid vaccine candidate: a phase 3 multicentre, observer-blind, randomised, controlled trial

Bruyn, Guy de; Gordon, David L.; Steiner, Theodore S.; Tambyah, Paul Ananth; Cosgrove, Catherine; Martens, Mark G.; Bassily, Ehab; Chan, Eng Soon; Patel, Dhaval; Chen, Josh; Torre‐Cisneros, Julián; Francesconi, Carlos Fernando de Magalhães; Gesser, Richard M.; Jeanfreau, Robert; Launay, Odile; Laot, Thelma; Morfín‐Otero, Rayo; Oviedo‐Orta, Ernesto; Park, Yoon Soo; Piazza, Franco M.; Rehm, Christine; Rivas, Enrique; Self, Steve; Gurunathan, Sanjay

doi:10.1016/s1473-3099(20)30331-5

Cited by 53 publications

(36 citation statements)

References 25 publications

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“…Another approach for primary prevention might be active immunisation. Although preclinical studies have been promising, a phase 3 C. difficile toxoid vaccine trial was terminated because of futility and clinical development of this vaccine candidate was stopped [276].…”

Section: Alternative Preventive Strategiesmentioning

confidence: 99%

European Society of Clinical Microbiology and Infectious Diseases: 2021 update on the treatment guidance document for Clostridioides difficile infection in adults

Prehn

Reigadas

Vogelzang

et al. 2021

Clinical Microbiology and Infection

360

320

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This is a PDF file of an article that has undergone enhancements after acceptance, such as the addition of a cover page and metadata, and formatting for readability, but it is not yet the definitive version of record. This version will undergo additional copyediting, typesetting and review before it is published in its final form, but we are providing this version to give early visibility of the article. Please note that, during the production process, errors may be discovered which could affect the content, and all legal disclaimers that apply to the journal pertain.

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Section: Alternative Preventive Strategiesmentioning

confidence: 99%

European Society of Clinical Microbiology and Infectious Diseases: 2021 update on the treatment guidance document for Clostridioides difficile infection in adults

Prehn

Reigadas

Vogelzang

et al. 2021

Clinical Microbiology and Infection

360

320

View full text Add to dashboard Cite

show abstract

“…The active group subsequently had 34 confirmed cases of CDI and the placebo group had 16, indicating no significant efficacy of the vaccine. 59 Due to futility this trial was terminated after an interim analysis. 59 …”

Section: Translation To Therapymentioning

confidence: 99%

Immune response against Clostridioides difficile and translation to therapy

Sehgal

Khanna

2021

Therap Adv Gastroenterol

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The pathogenesis of Clostridioides difficile infection (CDI) has largely been attributed to the action of two major toxins – A and B. An enhanced systemic humoral immune response against these toxins has been shown to be protective against recurrent CDI. Over the years, fully human monoclonal antibodies against both of these toxins have been developed in an attempt to counter the increasing incidence of recurrent CDI. Clinical trials conducted to evaluate the efficacy of anti-toxin A monoclonal antibody, actoxumab, and anti-toxin B monoclonal antibody, bezlotoxumab, demonstrated that bezlotoxumab substantially lowered the rate of recurrent infection, while actoxumab did not. A significant therapeutic benefit was appreciated in patients with at least one high-risk factor for recurrence, including, age ⩾65 years, immunocompromised state, prior CDI and severe CDI. In light of toxins A and B being immunogenic, vaccine trials are underway with the aim to prevent primary infection.

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“…While it has been reported that these vaccines may circumvent manifestations of the disease, they seem to be unable to prevent C. difficile colonization in the gastrointestinal tract, or sporulation or shedding of spores in the environment [ 59 , 60 ]. In a recent Phase 3 trial investigating a C. difficile toxoid vaccine candidate, the vaccine was not able to prevent infection and the trial was ended for futility [61] . Given the lack on an effective vaccine, current guidelines obviously do not include C. difficile vaccination among recommendations.…”

Section: Clostridium Difficilementioning

confidence: 99%

Vaccinations in patients with inflammatory bowel disease

Macaluso

Liguori

Galli

2021

Digestive and Liver Disease

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Treatment of inflammatory bowel disease (IBD) frequently requires administration of immunosuppressive therapies, which increases susceptibility to a number of infectious pathogens. However, many infections can be prevented by correct and appropriate utilization of vaccinations. While several guidelines have been published on vaccination schedules in patients with IBD, vaccination rates remain suboptimal and even lower than those in the general population. This is due to many factors including poor awareness of the importance of vaccines by gastroenterologists and general practitioners as well as potential prejudices of patients regarding the safety and benefits of vaccines. With the aim of increasing awareness about the key role of immunization in the management of patients with IBD, the present review examines the existing literature relating to the main vaccinations and their application in these patients. We also summarize current evidence in order to provide clinicians with an easy source of reference for the principal recommendations for prevention of infectious diseases in patients with IBD. In addition, the recommendations about traveling for IBD patients are briefly explored. Lastly, since it is important for gastroenterologists to be aware of recommendations on vaccination, we recommend implementing educational programs to ensure compliance with current guidelines.

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Safety, immunogenicity, and efficacy of a Clostridioides difficile toxoid vaccine candidate: a phase 3 multicentre, observer-blind, randomised, controlled trial

Cited by 53 publications

References 25 publications

European Society of Clinical Microbiology and Infectious Diseases: 2021 update on the treatment guidance document for Clostridioides difficile infection in adults

European Society of Clinical Microbiology and Infectious Diseases: 2021 update on the treatment guidance document for Clostridioides difficile infection in adults

Immune response against Clostridioides difficile and translation to therapy

Vaccinations in patients with inflammatory bowel disease

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