scholarly journals Recombinant Fusion Protein Vaccine Containing FliC and FliD Protects Mice Against Clostridioides Difficile Infection

2022 ◽  
Author(s):  
Shaohui Wang ◽  
Xianghong Ju ◽  
Keshan Zhang ◽  
Zhibian Duan ◽  
Hiran Malinda Lamabadu Warnakulasuriya Patabendige ◽  
...  
Keyword(s):  
Fusion Protein ◽  
Vaccine Candidate ◽  
Effective Vaccine ◽  
Protein Vaccine ◽  
Igg Antibody ◽  
Bacterial Flagella ◽  
Bacterial Proteins ◽  
Clostridioides Difficile ◽  
Clostridioides Difficile Infection ◽  
Flagellar Proteins

Abstract Bacterial flagella are involved in infection through their roles in host-cell adhesion, cell invasion, auto-agglutination, colonization, and formation of biofilms, as well as in the regulation and secretion of non-flagellar bacterial proteins involved in the virulence process. In this study, we constructed a fusion protein vaccine (FliCD) containing Clostridiodes difficile flagellar proteins FliC and FliD. Immunization of mice with FliCD induce potent IgG antibody responses against FliCD and protected mice against C. difficile infection and decrease C. difficile spores and toxin levels in the feces after infection. Furthermore, we found anti-FliCD serum protected mice against CDI and decreased C. difficile spores and toxin levels in the feces after C. difficile infection. Finally, we found that anti-FliCD serum inhibited the binding of C. difficile vegetative cells to HCT8 cells. These results imply that FliCD fusion protein may represent an effective vaccine candidate for the prevention from C. difficile infection (CDI).

scholarly journals A Novel Bacteriophage Lysin-Human Defensin Fusion Protein Is Effective in Treatment of Clostridioides difficile Infection in Mice

2019 ◽  
Vol 9 ◽  
Author(s):  
Zhong Peng ◽  
Shaohui Wang ◽  
Mussie Gide ◽  
Duolong Zhu ◽  
Hiran Malinda Lamabadu Warnakulasuriya Patabendige ◽  
...  
Keyword(s):  
Fusion Protein ◽  
Clostridioides Difficile ◽  
Clostridioides Difficile Infection

scholarly journals Invisible steps for a global endemy: molecular strategies adopted by Clostridioides difficile

2021 ◽  
Vol 14 ◽  
pp. 175628482110327
Author(s):  
Katia Fettucciari ◽  
Pierfrancesco Marconi ◽  
Andrea Marchegiani ◽  
Alessandro Fruganti ◽  
Andrea Spaterna ◽  
...  
Keyword(s):  
Epidemiological Data ◽  
Interferon Γ ◽  
Effective Vaccine ◽  
Clostridioides Difficile ◽  
Clostridioides Difficile Infection ◽  
Irritable Bowel ◽  
Factor Α ◽  
Selective Therapy ◽  
Enteric Glial Cell ◽  
Necrosis Factor

Clostridioides difficile infection (CDI) is on the rise worldwide and is associated with an increase in deaths and socio-health burden. C. difficile has become ubiquitous in anthropized environments because of the extreme resistance of its spores. Based on the epidemiological data and knowledge of molecular pathogenesis of C. difficile, it is possible to predict its progressive colonization of the human population for the following reasons: first, its global spread is unstoppable; second, the toxins (Tcds) produced by C. difficile, TcdA and TcdB, mainly cause cell death by apoptosis, but the surviving cells acquire a senescence state that favours persistence of C. difficile in the intestine; third, proinflammatory cytokines, tumour necrosis factor-α and interferon-γ, induced during CDI, enhance the cytotoxicity of Tcds and can increase the survival of senescent cells; fourth, Tcds block mobility and induce apoptosis in immune cells recruited at the infection site; and finally, after remission from primary infection or relapse, C. difficile causes functional abnormalities in the enteric glial cell (EGC) network that can result in irritable bowel syndrome, characterized by a latent inflammatory response that contributes to C. difficile survival and enhances the cytotoxic activity of low doses of TcdB, thus favouring further relapses. Since a ‘global endemy’ of C. difficile seems inevitable, it is necessary to develop an effective vaccine against Tcds for at-risk individuals, and to perform a prophylaxis/selective therapy with bacteriophages highly specific for C. difficile. We must be aware that CDI will become a global health problem in the forthcoming years, and we must be prepared to face this menace.

scholarly journals An adjuvanted subunit SARS-CoV-2 spike protein vaccine provides protection against Covid-19 infection and transmission

2021 ◽  
Author(s):  
Kairat Tabynov ◽  
Nurkeldi Turebekov ◽  
Meruert Babayeva ◽  
Gleb Fomin ◽  
Toktasyn Yerubaev ◽  
...  
Keyword(s):  
T Cell ◽  
Neutralizing Antibodies ◽  
Vaccine Candidate ◽  
T Cell Responses ◽  
Spike Protein ◽  
Effective Vaccine ◽  
Protein Vaccine ◽  
Wild Type ◽  
Cell Responses ◽  
Ongoing Development

Abstract Recombinant protein approaches offer major promise for safe and effective vaccine prevention of SARS-CoV-2 infection. We developed a recombinant spike protein vaccine (called NARUVAX-C19) and characterized its ability when formulated with a nanoemulsion adjuvant to induce anti-spike antibody and T-cell responses and provide protection including against viral transmission in rodent. In mice, NARUVAX-C19 vaccine administered intramuscularly twice at 21-day interval elicited balanced Th1/Th2 humoral and T-cell responses with high titers of neutralizing antibodies against wild-type (D614G) and delta (B.1.617.2) variants. In Syrian hamsters, NARUVAX-C19 provided complete protection against wild-type (D614G) infection and prevented its transmission to naïve animals placed in the same cage as challenged animals. The results contrasted with only weak protection seen with a monomeric spike receptor binding domain (RBD) vaccine even when formulated with the same adjuvant. These encouraging results warrant ongoing development of this Covid-19 vaccine candidate.

E7-NT-gp96 fusion protein vaccine enhances specific immune responses in mice model

2011 ◽  
Vol 44 (13) ◽  
pp. S46
Author(s):  
Elham Mohit ◽  
Azam Bolhassani ◽  
Farnaz Zahedifard ◽  
Mohammad Taghikhani ◽  
Eslamifar Ali ◽  
...  
Keyword(s):  
Immune Responses ◽  
Fusion Protein ◽  
Protein Vaccine ◽  
Mice Model

scholarly journals 1211. Response to Fecal Microbiota Transplant (FMT) in Refractory Clostridioides difficile Infection (CDI) is Modest Compared to Recurrent CDI in Hospitalized Patients

2020 ◽  
Vol 7 (Supplement_1) ◽  
pp. S627-S627
Author(s):  
Jae Hyun Shin ◽  
R Ann Hays ◽  
Cirle Warren
Keyword(s):  
Health System ◽  
Complete Resolution ◽  
Fecal Microbiota ◽  
Inpatient Setting ◽  
University Of Virginia ◽  
Cure Rate ◽  
Fecal Microbiota Transplant ◽  
Safety And Efficacy ◽  
Clostridioides Difficile ◽  
Clostridioides Difficile Infection

Abstract Background There are limited options for Clostridioides difficile infection (CDI) refractory to conventional antibiotic therapy (metronidazole, vancomycin, or fidaxomicin). Fecal microbiota transplant (FMT) is considered a safe and effective treatment for recurrent CDI but has not been widely utilized for refractory CDI due to concerns about safety. Even when included in studies, refractory CDI has not been analyzed separately from recurrent CDI. We reviewed cases of FMT performed in the inpatient setting for CDI to evaluate its safety and efficacy for refractory CDI. Methods Patients who received FMT inpatient at University of Virginia Health System for recurrent or refractory CDI after Infectious Diseases and Gastroenterology consultation signed informed consent acknowledging that FMT was considered investigational use in CDI not responding to standard of care as per 2014 FDA guidance. Charts were reviewed as part of quality improvement efforts to evaluate safety and efficacy of FMT in inpatient setting. Results Starting in July 2014, 13 patients received FMT for CDI as inpatients. Six received FMT for recurrent CDI, with four having complete resolution, one had recurrent CDI, and one had persistent C. difficile-negative diarrhea, for cure rate of 83%, comparable to published studies. Seven patients received FMT for refractory CDI, with three resulting in complete resolution. One responded to FMT but refused further care, one died from multiorgan failure after initial response to FMT that was possibly related to CDI, strongyloides, and/or CMV. Two patients had ongoing diarrhea suggestive of post-infectious irritable bowel syndrome, one was C. difficile-negative and one was not tested. The cure rate was 57%, lower than that of the recurrent CDI, but without any clear evidence of microbiologic failure. Outcome of patients undergoing FMT for CDI in the inpatient setting at University of Virginia Health System Conclusion Cure rate for FMT for refractory CDI was lower than recurrent CDI, but review of the cases of treatment failures did not reveal any microbiologic evidence of failure. FMT should be considered an alternative option when treating refractory CDI. Disclosures All Authors: No reported disclosures

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