Protective antibodies against <i>Clostridium difficile</i> are present in intravenous immunoglobulin and are retained in humans following its administration

Negm, Ola H.; MacKenzie, Brendon; Hamed, Magdy; Ahmad, Omar; Shone, Clifford C.; Humphreys, David P.; Acharya, K. Ravi; Loscher, Christine E.; Marszalowska, Izabela; Lynch, Mark; Wilcox, Mark H.; Monaghan, Tanya

doi:10.1111/cei.12946

Cited by 21 publications

(14 citation statements)

References 29 publications

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“…Although intra-venous gamma globulins (IVGG) have been tested in many patients with CDI, the results are varied and make recommendation for use difficult ( O’Horo and Safdar, 2009 ; Diraviyam et al, 2016 ). Negm et al (2017) observed differences in TcdA neutralizing efficacy between three commercial immunoglobulin preparations as well as differences in level of specific IgG isotypes against C. difficile antigens.…”

Section: Passive Immunizations Targeting C Difficile mentioning

confidence: 85%

Targeting Clostridium difficile Surface Components to Develop Immunotherapeutic Strategies Against Clostridium difficile Infection

et al. 2018

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New therapies are needed to prevent and treat Clostridium difficile infection and to limit the rise in antibiotic resistance. Besides toxins, several surface components have been characterized as colonization factors and have been shown as immunogenic. This review will focus on passive and active immunization strategies targeting C. difficile surface components to combat C. difficile. Concerning passive immunization, the first strategies used antisera raised against the entire bacterium to prevent infection in the hamster model. Then, surface components such as the flagellin and the S-layer proteins were used for immunization and the passive transfer of antibodies was protective in animal models. Passive immunotherapy with polyvalent immunoglobulins was used in humans and bovine immunoglobulin concentrates were evaluated in clinical trials. Concerning active immunization, vaccine assays targeting surface components were tested mainly in animal models, mouse models of colonization and hamster models of infection. Bacterial extracts, spore proteins and surface components of vegetative cells such as cell wall proteins, flagellar proteins, and polysaccharides were used as vaccine targets. Vaccine assays were performed by parenteral and mucosal routes of immunization. Both gave promising results and pave the way to development of new vaccines.

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Section: Passive Immunizations Targeting C Difficile mentioning

confidence: 85%

Targeting Clostridium difficile Surface Components to Develop Immunotherapeutic Strategies Against Clostridium difficile Infection

et al. 2018

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“…While the identification of pathogen-specific antibodies is a cornerstone of microbiologic diagnostics, a commercial assay for the serological confirmation of ongoing CDI is lacking. Several investigators have developed tests to evaluate the host humoral immune response to infection (38-40). An association has also been demonstrated between the humoral immune response to CD and infectious course (21).…”

Section: Discussionmentioning

confidence: 99%

Novel Immunoassay for Diagnosis of OngoingClostridioides difficileInfections Using Serum and Medium Enriched for Newly Synthesized Antibodies (MENSA)

Haddad¹,

Nozick²,

Kim³

et al. 2020

Preprint

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47BACKGROUND. Clostridioides difficile infections (CDI) have been a challenging and 48 increasing serious concern in recent years. While early and accurate diagnosis is crucial, available assays 49 have frustrating limitations 50 51 OBJECTIVE. Develop a simple, blood-based immunoassay to accurately diagnose patients 52 suffering from active CDI. 53 54 MATERIALS AND METHODS. Uninfected controls (n=95) and CDI patients (n=167) were 55 recruited from Atlanta area hospitals. Blood samples were collected from patients within twelve days of a 56 positive CDI test and processed to yield serum and PBMCs cultured to yield medium enriched for newly 57 synthesized antibodies (MENSA). Multiplex immunoassays measured Ig responses to ten recombinant C. 58 difficile antigens. 59 60 RESULTS. Sixty-six percent of CDI patients produced measurable responses to C. difficile 61 antigens in their serum or MENSA within twelve days of a positive CDI test. Fifty-two of the 167 CDI 62 patients (31%) were detectable in both serum and MENSA, but 32/167 (19%) were detectable only in 63 MENSA, and 27/167 (16%) were detectable only in serum. 64 65 DISCUSSION. We describe the results of a multiplex immunoassay for the diagnosis of ongoing 66 CDI in hospitalized patients. Our assay resolved patients into four categories: MENSA-positive only, 67 serum-positive only, MENSA-and serum-positive, and MENSA-and serum-negative. The MENSA 68 positive-only patients accounted for 30% and may be attributed to nascent antibody secretion in MENSA 69 prior to seroconversion. Conversely, the serum positive-only subset may have been more advanced in 70 5 5 their disease course. Immunocompromise and misdiagnosis may have contributed to the 34% of CDI 71 patients who were not identified using MENSA or serum immunoassays. 72 73 IMPORTANCE. While there was considerable overlap between patients identified through 74 MENSA and serum, both methods detected additional, unique patients. The combined use of both 75 MENSA and serum to detect CDI patients resulted in the greatest identification of CDI patients. Together, 76 longitudinal analysis of MENSA and serum will provide a more accurate evaluation of successful host 77 humoral immune responses in CDI patients. 78In this observational investigation, we present the results of a pilot study validating the use of a 127 multi-antigen immunoassay and its ability to measure antibody secretion reflecting ongoing CDI in 128 MENSA samples from a complex hospital population and compare its performance with results from sera. 129 130 RESULTS 131

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“…The approach of using specific IgY for prevention and treatment of CDI offers an alternative to current immunotherapies, which use intravenous administration of anti-TcdA and TcdB monoclonal human antibodies (Negm et al, 2017 ). To the best of our knowledge, there are no reported prophylactic therapies that target to prevent the initiation of CDI in a susceptible host by removing C. difficile spores from the host.…”

Section: Discussionmentioning

confidence: 99%

Characterization of Chicken IgY Specific to Clostridium difficile R20291 Spores and the Effect of Oral Administration in Mouse Models of Initiation and Recurrent Disease

Pizarro-Guajardo

Díaz-González

Álvarez-Lobos

et al. 2017

Front. Cell. Infect. Microbiol.

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Clostridium difficile infection (CDI) are the leading cause of world-wide nosocomial acquired diarrhea. The current main clinical challenge in CDI is the elevated rate of infection recurrence that may reach up to 30% of the patients, which has been associated to the formation of dormant spores during the infection. We sought to characterize the effects of oral administration of specific anti-spore IgY in mouse models of CDI and recurrent CDI. The specificity of anti-spore IgY was evaluated in vitro. In both, initiation mouse model and recurrence mouse model, we evaluated the prophylactic and therapeutic effect of anti-spore IgY, respectively. Our results demonstrate that anti-spore IgY exhibited high specificity and titers against C. difficile spores and reduced spore adherence to intestinal cells in vitro. Administration of anti-spore IgY to C57BL/6 mice prior and during CDI delayed the appearance of the diarrhea by 1.5 day, and spore adherence to the colonic mucosa by 90%. Notably, in the recurrence model, co-administration of anti-spore IgY coupled with vancomycin delayed the appearance of recurrent diarrhea by a median of 2 days. Collectively, these observations suggest that anti-spore IgY antibodies may be used as a novel prophylactic treatment for CDI, or in combination with antibiotics to treat CDI and prevent recurrence of the infection.

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Protective antibodies against Clostridium difficile are present in intravenous immunoglobulin and are retained in humans following its administration

Cited by 21 publications

References 29 publications

Targeting Clostridium difficile Surface Components to Develop Immunotherapeutic Strategies Against Clostridium difficile Infection

Targeting Clostridium difficile Surface Components to Develop Immunotherapeutic Strategies Against Clostridium difficile Infection

Novel Immunoassay for Diagnosis of OngoingClostridioides difficileInfections Using Serum and Medium Enriched for Newly Synthesized Antibodies (MENSA)

Characterization of Chicken IgY Specific to Clostridium difficile R20291 Spores and the Effect of Oral Administration in Mouse Models of Initiation and Recurrent Disease

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