Fecal Antibody Research Articles

Effectiveness and safety study of formula containing probiotics, prebiotics, synbiotics on fullterm infants' growth - a systematic review and meta-analysis of randomized controlled study.

Probiotics, prebiotics, and synbiotics, are hot topics of research and have been shown to improve the body's disease state and promote health. Analysis of whether infant formula containing probiotcs, prebiotics, synbiotics is beneficial to infant and child growth. We systematically searched multiple electronic databases (PubMed, Web of Science, The Cochrane Library, Embase) to identify eligible studies published from 1966 to December 25, 2022. Included studies were randomized controlled trials (RCTs) studying the influence of milk powder containing probiotcs, prebiotics, synbiotics on infants and children's growth. RevMan 5.4 was used to analyze the data. A total of 55 RCTs with a total sample size of 8868 participants met the inclusion criteria. Milk powder with probiotics, prebiotics, synbiotics does not significantly improve the growth of infants and children (Weight, height, BMI, and Head Circumference); The incidence of minor adverse events (OR 0.88, 95% CI 0.70-1.11 P = 0.28) and serious adverse events (OR 0.92, 95% CI 0.62-1.36 P = 0.67) was also comparable to the control group; The intestinal microbial diversity of infants consuming probiotcs, prebiotics, synbiotics supplemented formula was lower than that of infants consuming formula without probiotcs, prebiotics, synbiotics (SMD -0.88, 95% CI -1.66- -0.1 P = 0.03), but the abundance of individual beneficial flora was increased. (SMD 1.62, 95%CI 0.61-2.62 P = 0.002). In particular, the abundance of Lactobacillus (SMD 1.62, 95% CI 0.61-2.62 P = 0.002). For metabolites, synbiotics increased fecal antibody concentrations (SMD 0.47, 95% CI 0.08-0.86 P = 0.02), but fecal short-chain fatty acid concentrations remained balanced in both groups (SMD 0.05 95% CI -0.17-0.28 P = 0.64). Compared to the control group, infants who consumed formula with prebiotics had softer stools (SMD -1.47, 95% CI -2.23 to -0.7 P = 0.002) and lower stool pH (SMD -0.82, 95% CI -1.15- -0.5 P < 0.00001), there is also more frequency of bowel movements (SMD 0.27, 95% CI 0.09-0.44 P = 0.002). Probiotcs, prebiotics, synbiotics supplemented formulas significantly increased abundance of individual probiotics, alter intestinal antibody secretion, and improve bowel movements. Incidence of adverse reactions did not differ between the two groups. So we can choose formula-supplemented probiotcs, prebiotics, synbiotics to maintain the intestinal health of infants.

Early administration of canine parvovirus monoclonal antibody prevented mortality after experimental challenge.

To evaluate the effectiveness of canine parvovirus monoclonal antibody (CPMA) as a treatment against canine parvovirus (CPV-2)-induced mortality and to support USDA product licensure. 28 purpose-bred Beagle dogs aged 8 weeks were randomized to the treated (n = 21) or control (7) group. Dogs were challenged intranasally with 104.2 TCID50 virulent CPV-2b on Day 0 and monitored for 14 days for fecal viral shed and clinical disease. All dogs began shedding CPV-2 on Day 4 and were treated intravenously with a single dose of either CPMA (0.2 mL/kg) or saline (equal volume). No additional treatments were given to either group. Feces and sera were collected for quantitative analysis of fecal viral shed (hemagglutination) and antibody responses (hemagglutination inhibition and dot-blot ELISA), respectively. Dogs were monitored twice daily for parameters including lymphopenia, fever, vomiting, abnormal feces, inappetence, and lethargy. Humane endpoints triggered euthanasia by a veterinarian masked to treatment groups. The primary outcome variable was prevention of mortality as compared to controls. Mortality was prevented in all CPMA-treated dogs compared to 57% mortality in the control group (P = .0017, Fisher exact test). Canine parvovirus monoclonal antibody-treated dogs also experienced less severe and/or shorter durations of diarrhea, fever, vomiting, CPV-2 shedding in feces, and lymphopenia. Both groups showed similar immunoglobulin M responses as measured by semiquantitative analysis. Intravenous administration of CPMA can effectively improve clinical outcome when administered early in CPV-2 disease. Canine parvovirus monoclonal antibody treatment after proven infection does not interfere with adaptive immunity.

Impact of RYGB surgery on plasma immunoglobulins: association between blood pressure and glucose levels six months after surgery.

We aimed to study levels of natural antibodies in plasma, and their associations to clinical and fecal biomarkers, before and 6 months after Roux-en-Y gastric bypass (RYGB) surgery. Thirty individuals with obesity [16 type 2 diabetic, 14 non-diabetic (ND)] had RYGB surgery. Total plasma IgA, IgG and IgM antibody levels and specific antibodies to oxidized low-density lipoprotein (oxLDL), malondialdehyde-acetaldehyde adducts, Porphyromonas gingivalis gingipain A hemagglutinin domain (Rgp44), and phosphocholine were measured using chemiluminescence immunoassay. Associations between plasma and fecal antibodies as well as clinical markers were analyzed. RYGB surgery reduced blood pressure, and the glycemic state was improved. A higher level of diastolic blood pressure was associated with lower plasma antibodies to oxLDL after surgery. Also, lower level of glucose markers associated with lower level of plasma antibodies to bacterial virulence factors. Antibodies to oxLDL decreased after surgery, and positive association between active serum lipopolysaccharide and specific oxLDL antibodies was detected. Total IgG levels decreased after surgery, but only in ND individuals. Reduced level of total plasma IgG, improved state of hypertension and hyperglycemia and their associations with decreased levels of specific antibodies in plasma, suggest an improved state of systemic inflammation after RYGB surgery.

Total fecal IgA levels increase and natural IgM antibodies decrease after gastric bypass surgery.

Obesity is associated with low-grade inflammation and increased systemic oxidative stress. Roux-en-Y gastric bypass (RYGB) surgery is known to ameliorate the obesity-induced metabolic dysfunctions. We aimed to study the levels of natural antibodies in feces, before and 6 months after RYGB surgery in obese individuals with and without type 2 diabetes (T2D). Sixteen individuals with T2D and 14 non-diabetic (ND) individuals were operated. Total IgA, IgG and IgM antibody levels and specific antibodies to oxidized low-density lipoprotein (oxLDL), malondialdehyde-acetaldehyde adducts (MAA adducts), Porphyromonas gingivalis gingipain A hemagglutinin domain (Rgp44) and phosphocholine (PCho) were measured using chemiluminescence immunoassay. Total fecal IgA was elevated, while total IgM and IgG were not affected by the surgery. Fecal natural IgM specific to oxLDL decreased significantly in both T2D and ND individuals, while fecal IgM to Rgp44 and PCho decreased significantly in T2D individuals. A decrease in IgG to MAA-LDL, Rgp44 and PCho was detected. RYGB surgery increases the levels of total fecal IgA and decreases fecal natural IgG and IgM antibodies specific to oxLDL. Natural antibodies and IgA are important in maintaining the normal gut homeostasis and first-line defense against microbes, and their production is markedly altered with RYGB surgery.

Evaluating Salmonella pullorum dissemination and shedding patterns and antibody production in infected chickens

BackgroundPullorum disease caused by Salmonella pullorum is one of the most important infectious diseases in the poultry industry, responsible for causing substantial economic losses globally. On farms, the traditional method to detect S. pullorum infection mainly involves the collection of feces and sera to test for antigens and antibodies, respectively, but the regularity of Salmonella pullorum dissemination in internal organs and shedding patterns and antibody production in infected chickens remains unclear. Herein we aimed to investigate the dissemination of S. pullorum to different organs and bacterial shedding patterns in the faeces as well as serum antibody production post-infection in chickens of different ages.ResultIn this study, the liver and heart of 2-day-old chickens showed the highest copy numbers of S. pullorum at 6.4 × 106 and 1.9 × 106 copies of DNA target sequences/30 mg, respectively. In case of 10-day-old chickens, the percentage of S. pullorum fecal shedding (0%–40%) and antibody production (0%–56.6%) markedly fluctuated during the entire experiment; furthermore, in case of 42-week-old chickens, the percentage of birds showing S. pullorum shedding in the faeces showed a downward trend (from 63.33% to 6.6% in the oral inoculation group and from 43.3% to 10% in the intraperitoneal injection group), while that of birds showing serum antibody production remained at a high level (38.3% and 80% in the oral inoculation and intraperitoneal injection groups, respectively). We also performed cohabitation experiments, showed that 15% 10-day-old and 3.33% 42-week-old chickens were infected via the horizontal transmission in cohabitation with S. pullorum infected chickens, and revealed a high risk of horizontal transmission of S. pullorum.ConclusionThis study systematically evaluated the dissemination of S. pullorum in internal organs and bacterial fecal shedding patterns, and antibody production in infected chickens. Collectively, our findings indicate how to effectively screen S. pullorum-negative chickens on livestock farms and should also help in the development of measures to control and eradicate S. pullorum.

Compensatory intestinal antibody response against pro-inflammatory microbiota after bariatric surgery

ABSTRACT Obesity and type 2 diabetes (T2D) are growing burdens for individuals and the health-care system. Bariatric surgery is an efficient, but drastic treatment to reduce body weight, normalize glucose values, and reduce low-grade inflammation. The gut microbiome, which is in part controlled by intestinal antibodies, such as IgA, is involved in the development of both conditions. Knowledge of the effect of bariatric surgery on systemic and intestinal antibody response is limited. Here, we determined the fecal antibody and gut microbiome response in 40 T2D and non-diabetic (ND) obese individuals that underwent bariatric surgery (N = 40). Body weight, fasting glucose concentrations and inflammatory parameters decreased after bariatric surgery, whereas pro-inflammatory bacterial species such as lipopolysaccharide (LPS), and flagellin increased in the feces. Simultaneously, concentrations of LPS- and flagellin-specific intestinal IgA levels increased with the majority of pro-inflammatory bacteria coated with IgA after surgery. Finally, serum antibodies decreased in both groups, along with a lower inflammatory tone. We conclude that intestinal rearrangement by bariatric surgery leads to expansion of typical pro-inflammatory bacteria, which may be compensated by an improved antibody response. Although further evidence and mechanistic insights are needed, we postulate that this apparent compensatory antibody response might help to reduce systemic inflammation by neutralizing intestinal immunogenic components and thereby enhance intestinal barrier function after bariatric surgery.

Assessment of the Level of Interleukin IL 5 and IL 17 in Patients Infected with some Intestinal Parasites and H. pylori

The current study aimed to assess the level of interleukin IL 5 and IL 17 in patients infected with E. histolytica, G. lamblia parasites and H. pylori who suffer from diarrhea and some intestinal disorders, who attended Shirqat General Hospital / Salah al-Din Governorate, during the period from October 2020 to March 2021. The number of faecal samples examined was 409. The parasite infection were detected and investigated using direct wet smear and ether-formalin precipitation methods using light microscopy. All positive samples were examined for microscopic examination by antigen test for faecal samples and antibody test for rapid serum samples for detection of H. pylori co-infection of intestinal protozoa. The results showed that the total infection rate was 46 (11.24%) positive sample for the intestinal protozoa and 363 (88.7%) negative sample, E. histolytica was the higher with 67.38%, followed by Giardia lamblia with 32.61%. The results of the bacterial detection showed that 13 (28.26) positive samples and 33 (71.73%) negative samples, and the rate of co-infection between E. histolytica and H. pylori 9 (29.03%) was higher than the infection rate between Giardia lamblia and H. pylori 4 (26.66%). As for evaluating the level of Cytokines studied, the concentrations of some anti-inflammatory kinetics such as interleukin-5 and some pro-inflammatory kinetics such as interleukin-17 were estimated using ELISA technique. The results showed an increase in the concentration of interleukin-5 in the serum of patients with intestinal protozoa infections, as its concentration reached (10.956 ± 2.381 ml/Pg) compared to the control group (4.334 ± 1.434 ml/Pg), As for the patients infected with H. pylori (4.284±1.260 ml/Pg), there was no increase in the concentration of interleukin-5 compared to the control group (the healthy ones), While the concentration of IL-17 was lower in patients with intestinal protozoa infections (30.114 ± 4.877 ml/Pg) compared to the control group (35.665 ± 3.198 ml/Pg), As well as in patients infected with H. pylori bacteria (31.097±2.001 pg/ml) compared to the control group. The results of the statistical analysis showed that there were significant significant differences in the concentration of each of interleukin 5 and 17, which were statistically significant at the level of probability ≤ 0.01 P.

Seroprevalence and risk factors associated with Salmonella Dublin presence in Algerian dairy farms

Salmonella Dublin is a causative agent of a gastrointestinal bacterial infection prevalent in many cattle herds worldwide. Hence, the goal of this research was to evaluate the prevalence of Salmonella Dublin carriage in fecal and milk samples from dairy cattle from Algeria, and to investigate potential risk factors associated with the presence of S. Dublin antibodies. A total of 307 cows from 39 farms were analyzed in this study. Bacteriological and immunological methods were used to isolate and detect S. Dublin antibodies in feces and cow’s milk. Antimicrobial susceptibility testing was performed using the disc diffusion method. Logistic regression was used to study risk factors associated with S. Dublin antibodies. The bacteriological results showed the absence of S. Dublin and a prevalence of 0.97 % (3/307) (IC 95% 0 - 2.08)for S. Mbandaka. The immunological analysis of milk by the ELISA technique showed a prevalence of 36.33% (95% CI 30.44 - 42.22) for S. Dublin. Final multivariate regression models showed that the breed, the region and introduction of purchased cattle were associated with the presence of S. Dublin antibodies. This study is the first that reports the seroprevalence and risk factors associated with S. Dublin infection in Algeria and could be considered as a comparison point for further studies in Algeria.

Oral MucoRice-CTB vaccine for safety and microbiota-dependent immunogenicity in humans: a phase 1 randomised trial

There are an estimated 1·3-4·0 million cases of cholera and 20 000-140 000 cholera-related deaths worldwide each year. The rice-based cholera toxin B subunit (CTB) vaccine, MucoRice-CTB, is an oral candidate vaccine that does not require a cold chain, has shown efficacy in animal models, and could be of benefit in places where there is a paucity of medical infrastructure. We aim to assess the safety, tolerability, and immunogenicity of MucoRice-CTB in humans. We did a double-blind, randomised, placebo-controlled, dose-escalation, phase 1 study at one centre in Tokyo, Japan. Eligible participants were healthy adult men with measurable serum and faecal antibodies against CTB at screening. Participants were excluded if they had allergy to rice; history of cholera or travellers' diarrhoea; poorly controlled constipation; abnormal results on hepatic, renal, or haematological screening tests; use of any over-the-counter drugs within 7 days before first administration; inability to use a medically acceptable means of contraception; or other reasons by medical judgment of the investigator. Three dose cohorts of participants were randomly assigned by block to receive oral MucoRice-CTB (1 g, 3 g, or 6 g) or placebo (1 g, 3 g, or 6 g), once every 2 weeks for 8 weeks (for a total of 4 doses). The dose groups were performed sequentially, and each dose cohort was completed before the higher dose cohort began. All medical staff, participants, and most trial staff were masked to treatment allocation. The primary outcomes were safety and tolerability, measured by 12-lead electrocardiogram; vital signs; haematology, biochemistry, and urinalysis; rice protein-specific serum IgE antibody concentration; and monitoring of adverse events. Participants were assessed at baseline and at 1, 2, 4, 6, 8, and 16 weeks after the first administration of vaccine or placebo. The safety analysis set included all participants enrolled in the trial who received at least one dose of the study drug or placebo and were compliant with good clinical practice. The full analysis population included all participants enrolled in the trial who received at least one dose of the study drug and for whom any data were obtained after the start of study drug administration. Meta-genomic analysis of study participants was performed using bacterial DNA from faecal samples before vaccination. This trial is registered with UMIN.ac.jp, UMIN000018001. Between June 23, 2015, and May 31, 2016, 226 participants were recruited and assessed for eligibility. 166 participants were excluded based on health condition or schedule. We then randomly selected 60 male volunteers aged 20-40 years who were enrolled and assigned to MucoRice-CTB (10 participants assigned to 1 g, 10 participants assigned to 3 g, and 10 participants assigned to 6 g), or placebo (10 participants assigned to 1 g, 10 participants assigned to 3 g, and 10 participants assigned to 6 g). All participants received at least one dose of study drug or placebo and were included in the safety analyses. Two participants given MucoRice-CTB 3 g and one participant given MucoRice-CTB 6 g were lost to follow-up and excluded from the efficacy analysis. Serum CTB-specific IgG and IgA antibody concentrations in participants who received 6 g MucoRice-CTB increased significantly in both a time-dependent and dose-dependent manner compared with those in the placebo groups (p for interaction=0·002 for IgG, p=0·004 for IgA). Genome analysis of subjects' faeces before vaccination revealed that compared to non-responders, responders had a gut microbiota of higher diversity with the presence of Escherichia coli and Shigella spp. 28 (93%) of 30 participants who received MucoRice-CTB at any dose had at least one adverse event during the study period, compared with 30 (100%) of 30 participants given placebo. Grade 3 or higher adverse events were reported in four participants in the MucoRice-CTB group (5 events) and four participants in the placebo group (10 events). The most common serious adverse event was haemoglobin decreased (2 events in 2 participants in the pooled MucoRice-CTB group, 2 events in 2 participants in the placebo group; all grade 3). Participants given MucoRice-CTB showed increased CTB-specific serum IgG and IgA antibody concentrations without inducing serious adverse events, indicating that MucoRice-CTB could be a safe and potent vaccine to prevent diarrhoeal disease. MucoRice-CTB induced neutralising antibodies against diarrhoeal toxins in a gut microbiota-dependent manner. A similar phase 1 trial will be done with participants of other ethnicities to substantiate our findings. Translational Research Acceleration Network Program of Japan Agency for Medical Research and Development; Ministry of Education, Culture, Sports, Science and Technology, Japan; Science and Technology Research Partnership for Sustainable Development; Grant-in-Aid for Scientific Research (S) (18H05280) (to H K) from the Japan Society for the Promotion of Science (JSPS); Grant-in-Aid for Young Scientists (B) (16K16144) (to Y K) from JSPS; Grant-in-Aid for Young Scientists (18K18148) (to Y K) from JSPS; Grant from International Joint Usage/Research Center (K3002), the Institute of Medical Science, University of Tokyo.

Design and Production of Engineered Sta Toxin as a Vaccine Candidate Against Enterotoxigenic Escherichia coli

Introduction: Enterotoxigenic E. coli (ETEC) is one of the major causes of watery diarrhea outbreaks in children under five years of age and passengers in developing countries. The pathogenicity of ETEC is due to the secretion of Colonization factors (Cfs) and two enterotoxins including heat-labile (Lt) and heat-stable (St). Although diarrhea is considered as one of the causes of mortality in developing countries, no approved vaccine is available for the disease caused by ETEC. Accordingly, the objective of the present study was to design a vaccine candidate containing Sta toxin which accounts for 30-75% of ETEC species. Materials and Methods: A chimeric construct consisting of two Sta toxoid connected together by two linkers was designed. After expression and purification by Ni-NTA column, western blotting was performed to confirm the protein. The 2Sta protein was administered to BALB/c mice via injection and the serum and fecal antibodies titer was evaluated by the ELISA test. Results: The recombinant 2Sta protein was expressed in an insoluble form (inclusion body) and the 20 kDa band was observed on the SDS-PAGE 12%. The results of the ELISA test suggested that IgG and IgA antibodies had enhanced compared to the control group. Conclusions: The Sta protein which was produced in most ETEC species can be induced in the immune system and raised the serum and fecal antibodies. Using this candidate subunit vaccine could actually protect bacterial infection.

TARGETING SIDEROPHORES TO REDUCE COLONIZATION OF ADHERENT INVASIVE E. COLI IN CROHN’S DISEASE

Abstract The pathovar adherent-invasive Escherichia coli (AIEC) is a mucosa-associated bacterium that is frequently found in patients with Crohn’s disease (CD), but targeted treatment options are currently lacking. During intestinal inflammation, host-mediated iron limitation is a key strategy to restrict the outgrowth of pathogens. Various bacterial pathogens evade this nutrient limitation by secreting small, iron-chelating molecules known as siderophores. The siderophore enterobactin (Ent) is an important virulence factor for Gram-negative pathogens such as AIEC by promoting their expansion and competition over commensal microbes during colitis. Here, we developed an immunization-based approach to target bacterial siderophores during colitis and to reduce AIEC colonization in mice. We demonstrate that immunization with Ent (conjugated to the mucosal adjuvant cholera toxin subunit B, CTB) potently elicits fecal antibodies against Ent. Immunized animals show reduced AIEC colonization along with milder weight loss, less colonic shortening, and decreased histological severity scores. This phenotype is largely B cell-dependent, as immunized mice lacking mature B lymphocytes do not show protection during AIEC infection. Ent-specific B cells are primarily found in small intestinal Peyer’s patches and can be isolated by a flow cytometry-based sorting approach. This project paves the way to develop monoclonal antibodies against siderophores, which could provide a more targeted and narrow-spectrum strategy to reduce AIEC colonization in patients with CD.

Changes in the Intestinal Microbiota and Systemic Immune Responses by Dietary 1-Kestose Supplementation in Healthy Dogs

1-Kestose is a trisaccharide prebiotic that modifies immune responses in humans and rodents with allergic diseases by altering the intestinal microbiota. In the present study, we examined the effects of 1-kestose supplementation on the intestinal microbiota, peripheral lymphocyte subsets, and antibody production in healthy dogs. Fecal IgA levels and serum antibody titers against the rabies vaccine were not significantly affected by 1-kestose supplementation. In a flow cytometric analysis, the percentage of T cells among total lymphocytes decreased, whereas that of B cells increased in supplemented dogs. A metagenomic analysis of the intestinal microbiota showed that the proportion of Bifidobacterium increased, while that of Lactobacillus did not decrease in supplemented dogs. Furthermore, a quantification analysis using real-time polymerase chain reaction showed that the proportion of Bifidobacterium increased in supplemented dogs. These results suggest that 1-kestose supplementation induced modifications in the intestinal microbiota of dogs, which presumably enhanced the immune system. 1-Kestose may be a useful food material as a prebiotic for dogs.

Development of an Antigen Delivery Platform Using Lactobacillus acidophilus Decorated With Heterologous Proteins: A Sheep in Wolf's Clothing Story.

S-layers are bacterial structures present on the surface of several Gram-positive and Gram-negative bacteria that play a role in bacterial protection. In Lactobacillus acidophilus (L. acidophilus ATCC 4356), the S-layer is mainly composed of the protein SlpA. A tandem of two copies of the protein domain SLP-A (pfam: 03217) was identified at the C-terminal of SlpA, being this double SLP-A protein domain (in short dSLP-A) necessary and sufficient for the association of the protein to the L. acidophilus cell wall. A variety of proteins fused to the dSLP-A domain were able to spontaneously associate with high affinity to the cell wall of L. acidophilus and Bacillus subtilis var. natto, in a process that we termed decoration. Binding of dSLP-A-containing-proteins to L. acidophilus was stable at conditions that mimic the gastrointestinal transit in terms of pH, proteases, and bile salts. To evaluate if protein decoration of L. acidophilus can be adapted to generate an oral vaccine platform, a chimeric antigen derived from the bacterial pathogen Shiga-toxin-producing Escherichia coli (STEC) was constructed by fusing the sequences encoding the polypeptides EspA36–192, Intimin653–953, Tir240–378, and H7 flagellin352–374 (EITH7) to the dSLP-A domain (EITH7-dSLP-A). Recombinantly expressed EITH7-dSLP-A protein was affinity purified and combined with L. acidophilus cultures to allow the association of the chimeric antigen to the bacterial surface. EITH7-decorated L. acidophilus was orally administered to BALB/c mice and the induction of anti-EITH7 specific antibodies in sera and feces determined by ELISA. Mice presenting significantly higher anti-EITH7 antibodies titers were able to control more efficiently an experimental STEC infection than mice that received the non-decorated L. acidophilus carrier, indicating that antigen-decorated L. acidophilus can be adapted as a mucosal immunization delivery platform to elicit a protective immune response for vaccine purposes.

S0820 Real World Comparison of Bio-Originator Infliximab vs the Biosimilar Infliximab-abda in the Treatment of Inflammatory Bowel Disease

INTRODUCTION: Biologic therapies are indicated for the management of moderate-to-severe inflammatory bowel disease (IBD), including both Crohn’s disease (CD) and Ulcerative Colitis (UC). Biosimilars, biologic compounds that are similar but not identical to originator biologic therapies, have been developed for the management of a variety of immune mediated inflammatory disorders, including IBD, with similar efficacies and safety profiles to bio-originators. The primary aim of this study is to evaluate the efficacy and safety of biosimilars in IBD patients who were authorized for a non-medical switch from bio-originator infliximab to biosimilar infliximab-abda compared to patients who were maintained on originator therapy at the Cleveland Clinic. METHODS: This prospective observational cohort study was approved on 12/4/2019 by the institutional review board. IBD patients receiving infliximab and infliximab-abda infusions from 2018-2019 were identified. These charts were reviewed for characteristics listed in Table 1; surrogate markers of disease were used as noted in the table. Comparisons were made between cohorts using non-parametric testing for continuous variables and categorical variables (Table 1). A P-value of ≤0.05 was considered significant. RESULTS: Between Jan 2018 and Dec 2019, 359 patients were identified. 99 were switched from infliximab to infliximab-abda and 101 were continued on infliximab. Baseline demographics were similar between the two groups (Table 1). Both the infliximab-abda and infliximab groups had a higher proportion of patients with CD than UC at 63.6% and 74.3%, respectively. There was no significant difference in the use of corticosteroid taper and maintenance, fecal calprotectin, infliximab concentrations, and antibody levels. Although there was a significant difference in the CRP between patients that were switched compared to patients maintained on bio-originator, the differences are not clinically significant. Emergency department visits and inpatient admissions were similar between the two groups. Similar paired comparisons between patients pre- and post-switch showed no significant differences (Table 2). CONCLUSION: In a large cohort of patients receiving infusions at the Cleveland Clinic, our study demonstrates that a non-medical switch from bio-originator infliximab to biosimilar infliximab-abda was as safe and efficacious as continuing bio-originator therapy for IBD.Table 1.: Patients Switched to Infliximab-abda versus Patients Continued on InfliximabTable 2.: Patients Switched From Infliximab to Infliximab-abda As Self-Controls

Protective Passive Immunity in Escherichia coli ETEC-Challenged Neonatal Mice Conferred by Orally Immunized Dams with Nanoparticles Containing Homologous Outer Membrane Vesicles.

Enterotoxigenic Escherichia coli (ETEC) strains are a major cause of illness and death in mammals, including neonatal, recently weaned pigs and infant human beings. We have previously shown that outer membrane vesicles (OMV) obtained from ETEC serotypes encapsulated into zein nanoparticles, coated with a Gantrez-mannosamine polymer conjugate (OMV-NP), were immunogenic in mice and sows. In the present study, we show that pups from vaccinated mice were protected against ETEC F4 serotype challenge through maternal passive immunization. OMV from F4 cultures were collected and characterized. Two-week-pregnant BALB/c mice were orally immunized with a single dose of vesicles (0.2 mg) either free (OMV) or encapsulated into nanoparticles (OMV-NP). Evaluation of the antibodies in serum (IgG1, Ig2a or IgA) and feces (IgA) of dams immunized with OMV-NP revealed an enhancement of specific immunogenicity. The antibody response conferred by the nanoparticle adjuvant was also correlated with IL-6 and IL-10 splenic levels. Each mother was allowed to feed her progeny for one week. Suckling pups presented specific IgA in feces demonstrating their passive immunization through colostrum intake. Two weeks after the pups were born, they were infected orally with a single dose of F4 E. coli (1.2 × 108 CFU/pup). Results showed that 70% of the pups from dams immunized with OMV-NP were protected. In contrast, 80% of the pups from dams immunized with free OMV died as a result of the experimental challenge. These findings support the use of zein nanoparticles coated with a Gantrez-mannosamine shield as adjuvant delivery system for the oral immunization during pregnancy to confer immunity to the offspring through maternal immunization

Lungworm: A roundtable discussion

Lungworm (Angiostrongylus vasorum) is increasingly recognised as a cause of illness, particularly cardiorespiratory signs and haemorrhage, in dogs. It is now distributed across the UK, although prevalence varies widely and there are local foci of higher infection. Presentation of clinical cases varies considerably, and lungworm should be on many differential diagnosis lists. Diagnostic tests now include direct faecal smear, Baermann's, bronchoalveolar lavage, antibody and antigen ELISAs and PCR. Appropriate testing depends on the clinical situation, and no test is 100% sensitive and 100% specific. Treatment involves moxidectin or milbemycin oxime, plus supportive care. Tranexamic acid and plasma transfusions may both be useful in dogs showing coagulopathies. Dogs may be at risk from accidental ingestion of intermediate host slugs with grass, or larvae in puddles, as well as from deliberately eating slugs, so prevention relies heavily on monthly appropriate anthelmintics, and compliance is an issue in this. Other lungworm species also occur and should not be forgotten. In cats, the lungworm Aelurostrongylus abstrusus can cause severe, even fatal, infection and this is probably under-diagnosed. Monthly preventative treatment with a licensed product is recommended in cats that go outside.

Intradermal or Sublingual Delivery and Heat-Labile Enterotoxin Proteins Shape Immunologic Responses to a CFA/I Fimbria-Derived Subunit Antigen Vaccine against Enterotoxigenic Escherichia coli.

Enterotoxigenic Escherichia coli (ETEC) is a major cause of infectious diarrhea in children, travelers, and deployed military personnel. As such, development of a vaccine would be advantageous for public health. One strategy is to use subunits of colonization factors combined with antigen/adjuvant toxoids as an ETEC vaccine. Here, we investigated the intradermal (i.d.) or sublingual (s.l.) delivery of CFA/I fimbrial antigens, including CfaEB and a CfaE-heat-labile toxin B subunit (LTB) chimera admixed with double mutant heat-labile toxin (LT) LT-R192G/L211A (dmLT). In addition, we compared dmLT with other LT proteins to better understand the generation of adjuvanted fimbrial and toxoid immunity as well as the influence on any local skin reactogenicity. We demonstrate that immunization with dmLT admixed with CfaEB induces robust serum and fecal antibody responses to CFA/I fimbriae and LT but that i.d. formulations are not optimal for s.l. delivery. Improved s.l. vaccination outcomes were observed when higher doses of dmLT (1 to 5 μg) were admixed with CfaEB or, even better, when a CfaE-LTB chimera antigen was used instead. Serum anti-CFA/I total antibodies, detected by enzyme-linked immunosorbent assay, were the best predictor of functional antibodies, based on the inhibition of red blood cell agglutination by ETEC. Immunization with other LT proteins or formulations with altered B-subunit binding during i.d. immunization (e.g., by addition of 5% lactose, LTA1, or LT-G33D) minimally altered the development of antibody responses and cytokine recall responses but reduced skin reactogenicity at the injection site. These results reveal how formulations and delivery parameters shape the adaptive immune responses to a toxoid and fimbria-derived subunit vaccine against ETEC.

Aryl hydrocarbon receptor activation does not impact the number of myeloid-derived suppressor cells in the spleens of mice immunized with cholera toxin

Abstract The aryl hydrocarbon receptor (AhR) is a ligand-activated transcription factor that regulates immune responses. Previous studies in this laboratory have found that AhR activation with 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) in mice suppresses the anti-cholera toxin (CT) IgA response, but fecal antibody levels recover at least two weeks earlier than serum levels after repeated immunization. Studies by others have shown that TCDD exposure increases splenic myeloid-derived suppressor cell (MDSC) numbers in mice, and MDSC have been associated with enhanced IgA responses. In this study, we hypothesized that TCDD exposure would increase MDSC numbers in CT-immunized mice. Female C57Bl/6 mice were administered peanut oil (vehicle) or TCDD (40 μg/Kg) orally on day 0, and each animal was orally immunized with cholera toxin (CT, 10 μg/Kg) on days 1 and 8. On day 14, CT-specific serum IgA levels (ELISA) were significantly suppressed by TCDD exposure to 21.6% of control (P &amp;lt; 0.05), but fecal IgA levels were not significantly different. Total spleen cell numbers were significantly reduced by TCDD exposure to 72.9% of control (P &amp;lt; 0.05), but neither the percent nor number of MDSC (CD11b+ Gr1+, by flow cytometry) per spleen was significantly altered: 2.21% ± 0.48% and 1.91% ± 0.23% (450,000 ± 98,000 and 290,000 ± 34,000) for control and TCDD-treated, respectively (mean ± SEM). These results suggest that AhR activation differentially impacts antigen-specific IgA responses between serum and feces in cholera toxin-immunized mice, but not the number of MDSCs.

Association of MHC class II haplotypes with reduced faecal nematode egg count and IgA activity in British Texel sheep.

Nematode infection is one of the principal diseases suffered by sheep and the class II region of the MHC has been repeatedly associated with differences in susceptibility and resistance to infection. The aim of this study was to examine the association of MHC class II haplotypes in a flock of Texel sheep with faecal egg counts and antibody responsiveness. Two haplotypes carried the DRB1*11:01 allele which has previously been associated with reduced egg counts in Scottish Blackface and Suffolk sheep. One of the two haplotypes was associated with reduced egg counts in the Texel breed, and both haplotypes were associated with reduced IgA activity against an extract from fourth-stage larvae. The reduced IgA activity is probably a consequence of reduced numbers of fourth-stage larvae in sheep carrying the resistance allele. The association of specific MHC alleles with reduced egg counts, reduced worm numbers and decreased IgA activity provides a mechanism for the density-dependent regulation of parasite growth and fecundity.

Management of adult Clostridium difficile digestive contaminations: a literature review.

Clostridium difficile infections (CDI) dramatically increased during the last decade and cause a major public health problem. Current treatments are limited by the high disease recurrence rate, severity of clinical forms, disruption of the gut microbiota, and colonization by vancomycin-resistant enterococci (VRE). In this review, we resumed current treatment options from official recommendation to promising alternatives available in the management of adult CDI, with regard to severity and recurring or non-recurring character of the infection. Vancomycin remains the first-line antibiotic in the management of mild to severe CDI. The use of metronidazole is discussed following the latest US recommendations that replaced it by fidaxomicin as first-line treatment of an initial episode of non-severe CDI. Fidaxomicin, the most recent antibiotic approved for CDI in adults, has several advantages compared to vancomycin and metronidazole, but its efficacy seems limited in cases of multiple recurrences. Innovative therapies such as fecal microbiota transplantation (FMT) and antitoxin antibodies were developed to limit the occurrence of recurrence of CDI. Research is therefore very active, and new antibiotics are being studied as surotomycin, cadazolid, and rinidazole.