Abstract: Methods for treating coronavirus disease 2019 (COVID-19), the disease caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infections, are described. The methods can be used to reduce the severity of outcomes related to COVID-19, such as hospitalization and ventilation. For example, the methods can involve treatment of a subject with a therapeutic agent that degrades hyaluronan and/or an agent that neutralizes a hyaluronan receptor, e.g., CD44, such as an anti-CD44 antibody.

Abstract: Methods for treating coronavirus disease 2019 (COVID-19), the disease caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infections, is described. The methods can be used to reduce the severity of outcomes related to COVID-19, such as hospitalization and ventilation. For example, treatment of a subject with a therapeutic agent that neutralizes interleukin 13 (IL-13) can result in reduced risk for mechanical ventilation in the subject. Also described are methods of predicting risk of mechanical ventilation in subjects with COVID-19.

Abstract: Methods and compositions for treating or preventing C. difficile infections, particularly recurring C. difficile infections are described. The compositions for use in treating C. difficile include at least one agent that enhances a biological activity of interleukin-13 (IL-13), such as a recombinant IL-13 peptide or an agent that neutralizes the interleukin-13 (IL-13) decoy receptor, interleukin-13 receptor subunit alpha-2 (IL-13Ra2). Additionally or alternatively, the compositions can include a interleukin-4 (IL-4) peptide. The methods can result in more rapid recovery from CDI and decreased weight loss, e.g., than treatment without the neutralizing agent.

Abstract: Clostridium difficile infection is the leading cause of hospital acquired antibiotic-associated diarrhea in the US (Bartlett, in 2006). The increased prevalence of circulating C. difficile strains poses a significant health threat to US health care facilities. Strains expressing the toxin C. difficile Transferase (CDT), in addition to Toxins A and B (TcdA and TcdB), are more virulent and are associated with higher mortality rates (Bacci et al., 2011). We recently identified a protective role for eosinophils against C. difficile pathogenesis (Buonomo et al., 2016). We have also defined CDT's ability to increase host inflammation and suppress protective eosinophils through a TLR2 dependent mechanism (Cowardin et al., 2016). How CDT promotes virulence and eosinophil suppression via TLR2 is still under investigation.

Abstract: Clostridium difficile infection is the leading cause of hospital acquired antibiotic-associated diarrhea in the US (Bartlett, in 2006). The increased prevalence of circulating C. difficile strains poses a significant health threat to US health care facilities. Strains expressing the toxin C. difficile Transferase (CDT), in addition to Toxins A and B (TcdA and TcdB), are more virulent and are associated with higher mortality rates (Bacci et al., 2011). We recently identified a protective role for eosinophils against C. difficile pathogenesis (Buonomo et al., 2016). We have also defined CDT's ability to increase host inflammation and suppress protective eosinophils through a TLR2 dependent mechanism (Cowardin et al., 2016). How CDT promotes virulence and eosinophil suppression via TLR2 is still under investigation.

Abstract: Clostridium difficile is the most common hospital acquired pathogen in the United States, and infection is in many cases fatal. Toxins A and B are its major virulence factors, but increasingly a third toxin may be present, known as C. difficile transferase (CDT). An ADP-ribosyltransferase that causes actin cytoskeletal disruption, CDT is typically produced by the major, hypervirulent strains and has been associated with more severe disease. It is disclosed herein that CDT enhances the virulence of two PCR-ribotype 027 strains in mice. The toxin induces pathogenic host inflammation via a novel Toll-like Receptor 2 (TLR2) dependent pathway, resulting in the suppression of a protective host eosinophilic response. Finally, it is disclosed that restoration of TLR2 deficient eosinophils is sufficient for protection from a strain producing CDT. These findings offer an explanation for the enhanced virulence of CDT-expressing C.

Abstract: The present invention encompasses compositions and methods useful to treat or prevent Clostridium difficile antibiotic-associated colitis through administration of IL-25 and/or downstream cytokines IL-13, IL-4, and IL-5. It is disclosed herein that IL-25 expression is decreased during antibiotic treatment and during bacterial infection and that treatment with IL-25 protein is protective during infection. It is further disclosed herein the unexpected result that IL-25 treatment protects against C. difficile-associated mortality and morbidity. The present application further describes an unexpected result regarding eosinophils and their role in combating infection and their relationship to the effectiveness of IL-25.

Abstract: The present invention encompasses compositions and methods useful to treat or prevent Clostridium difficile antibiotic-associated colitis through administration of IL-25 and/or downstream cytokines IL-13, IL-4, and IL-5. It is disclosed herein that IL-25 expression is decreased during antibiotic treatment and during bacterial infection and that treatment with IL-25 protein is protective during infection. It is further disclosed herein the unexpected result that IL-25 treatment protects against C. difficile-associated mortality and morbidity. The present application further describes an unexpected result regarding eosinophils and their role in combating infection and their relationship to the effectiveness of IL-25.

Abstract: Clostridium difficile is the most common hospital acquired pathogen in the United States, and infection is in many cases fatal. Toxins A and B are its major virulence factors, but increasingly a third toxin may be present, known as C. difficile transferase (CDT). An ADP-ribosyltransferase that causes actin cytoskeletal disruption, CDT is typically produced by the major, hypervirulent strains and has been associated with more severe disease. It is disclosed herein that CDT enhances the virulence of two PCR-ribotype 027 strains in mice. The toxin induces pathogenic host inflammation via a novel Toll-like Receptor 2 (TLR2) dependent pathway, resulting in the suppression of a protective host eosinophilic response. Finally, it is disclosed that restoration of TLR2 deficient eosinophils is sufficient for protection from a strain producing CDT. These findings offer an explanation for the enhanced virulence of CDT-expressing C.

Abstract: The present invention relates to methods for the diagnosis, treatment and prevention of infectious and/or inflammatory diarrhea.

Abstract: The 170 kDa adhesin subunit of the Entamoeba histolytica Gal/GalNAc adherence lectin is encoded by members of a gene family that includes hgl1, hgl2 and a newly discovered gene, hgl3. The DNA and encoded protein sequences of the hgl genes are disclosed. A number of proteins and peptide fragments of the adhesin as well as other functional derivatives, preferably produced by recombinant methods in prokaryotic cells are disclosed. A preferred peptide for a vaccine composition corresponds to amino acids 896-998 of the mature 170 kDa lectin and contains the galactose- and N-acetylgalactosamine-binding activity of the native lectin. These compositions are useful as immunogenic vaccine components and as diagnostic reagents. Methods are provided for a vaccine comprising one or more peptides of the lectin to immunize subjects at risk for infection by E. histolytica. Additionally, immunoassay methods are disclosed for measuring antibodies specific for an epitope of the lectin. These methods detect E.

Abstract: The invention provides methods for expressing foreign genes in enteric protozoa. This transfection system was established using a gene ligated to the 5' and 3' flanking DNA regions of a protein-encoding gene from an enteric protozoa. The present invention also provides such transformed enteric protozoa, vaccines produced therefrom and foreign or altered proteins expressed in the same. The ability to introduce and express genes in amebae will now permit both genetic analysis and modification of the virulence of this organism, which remains a serious threat to world health and will facilitate basic research towards the control of this parasite.

Abstract: The invention provides methods for expressing foreign genes in enteric protozoa. This transfection system was established using a gene ligated to the 5' and 3' flanking DNA regions of a protein-encoding gene from an enteric protozoa. The present invention also provides such transformed enteric protozoa, vaccines produced therefrom and foreign or altered proteins expressed in the same. The ability to introduce and express genes in amebae will now permit both genetic analysis and modification of the virulence of this organism, which remains a serious threat to world health and will facilitate basic research towards the control of this parasite.

Abstract: A simple immunoassay method is provided which distinguishes pathogenic from nonpathogenic forms Entamoeba histolytica in biological samples. This assay utilizes monoclonal antibody preparations which are specific for designated epitopes of the 170 kd subunit of the Gal/GalNAc lectin. When pathogenic forms, specifically, are to be detected, at least one antibody which is immunospecific for an epitope unique to the forms of the 170 kd lectin found in pathogenic strains is used in the assay. The invention further includes monoclonal antibodies which are immunospecific for epitopes 1-3 of the 170 kd subunit of the Gal/GalNAc lectin of either pathogenic or nonpathogenic forms and to monoclonal antibodies specifically immunoreactive with epitopes unique to nonpathogenic derived 170 kd subunit, as well as purified forms of the Gal/GalNAc lectin from both pathogenic and nonpathogenic forms.

Abstract: A method to prepare a monoclonal antibody (mAb) specifically immunoreactive with an epitope of the Gal/GalNAc lectin of a pathogenic or nonpathogenic E. histolytica, or the 70 kd subunit thereof, is provided. This method comprises culturing an immortalized cell line capable of secreting the mAbs, where the cell line is obtained by immortalizing antibody-producing cells from a mammal immunized with a purified 170 kd subunit, or with purified Gal/GalNAc lectin of a pathogenic E. histolytica. The supernatants of the cells are screened for the presence or absence of antibodies specific for the subunit or lectin from a pathogenic E. histolytica and from a pathogenic E. histolytica, so as to determine the pathogen/nonpathogen specificity of the monoclonal antibody. Antibodies produced by this method and epitopes with which they react on pathogenic and/or nonpathogenic E. histolytica also are disclosed.

Abstract: A simple immunoassay method is provided which distinguishes pathogenic from nonpathogenic forms Entamoeba histolytica in biological samples. This assay utilizes monoclonal antibody preparations which are specific for designated epitopes of the 170 kd subunit of the Gal/GalNAc lectin. When pathogenic forms, specifically, are to be detected, at least one antibody which is immunospecific for an epitope unique to the forms of the 170 kd lectin found in pathogenic strains is used in the assay. The invention further includes monoclonal antibodies which are immunospecific for epitopes 1-3 of the 170 kd subunit of the Gal/GalNAc lectin of either pathogenic or nonpathogenic forms and to monoclonal antibodies specifically immunoreactive with epitopes unique to nonpathogenic derived 170 kd subunit, as well as purified forms of the Gal/GalNAc lectin from both pathogenic and nonpathogenic forms.

Abstract: Purified Gal/GalNAc adherence lectin of Entamoeba histolytica is used for development of a vaccine to prevent human amebiasis.