University of Virginia Patent Foundation

Infectious Disease Research Institute

Access To Advanced Health Institute

William A Petri

Barbara J Mann

Darrick Carter

Christopher B Fox

Neal Van Hoeven

Susan S Lin

Mayuresh M Abhyankar

Jay E Purdy

R Randolph Vines

James M Dodson

Alyse Longtin Frisbee

Carrie Adeline Cowardin

Erica Buonomo

Provided herein are PEGylated liposomes, and methods of making and using thereof. The PEGylated liposomes comprise at least a cholesterol, a non-PEGylated neutral lipid, and a PEGylated lipid, wherein the average molecular weight of the PEG component in the PEGylated lipid is about 5000 Daltons or less. The PEGylated liposomes are stable and capable of delivery of an agent for the generation of an immune response, for example an agent for vaccine, therapeutic, or diagnostic uses. Compositions and methods related to making the PEGylated liposomes and using the PEGylated liposomes for stimulating an immune response are also provided.

Pegylated liposomes and methods of use

PEGylated liposomes and methods of use

infection is the leading cause of hospital acquired antibiotic-associated diarrhea in the US (Bartlett, in 2006). The increased prevalence of circulatingstrains poses a significant health threat to US health care facilities. Strains expressing the toxinTransferase (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 againstpathogenesis (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. We employed a genome-wide microarray approach to reveal divergent transcriptional profiles between protected (TLR2&#x2212;/&#x2212;) and unprotected (WT) mice infected with either CDT expressing or CDT mutant strains of. This work revealed novel host mediated TLR2-dependent inflammatory pathways to CDT. We provide an unbiased framework for understanding the host immune response to the binary toxin CDT produced byand how TLR2 signaling enhances virulence.

Compositions and methods for treating clostridium difficile infection

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 astransferase (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-expressingand demonstrate a mechanism by which this binary toxin subverts the host immune response.

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The present invention encompasses compositions and methods useful to treat or preventantibiotic-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-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.

Compositions and methods for preventing and treating infection

The 170 kDa adhesin subunit of the,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,. Additionally, immunoassay methods are disclosed for measuring antibodies specific for an epitope of the lectin. These methods detect,-specific antibodies, some of which are specific for epitopes characteristic of pathogenic strains, nonpathogenic strains, or both.

Recombinant Entamoeba histolytica lectin subunit peptides and reagents specific for members of the 170 kDa subunit multigene family

Recombinant Entamoeba histolytica lectin subunit peptides and reagents

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.

Transfection of enteric parasites

cDNA encoding the 170 kd subunit of Gal/GalNAc lectin in various strains of E. histolytica is provided. Availability of this cDNA permits the use of diagnostic assays to distinguish pathogenic from nonpathogenic strains based on DNA hybridization, and further permits antisense approaches to interrupting the production of this lectin.

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Charlottesville, VA, United States of America

William A Petri