University of Pittsburgh

Akzo Nobel N.v.

Other

Akzo Nobel

Ronald C Montelaro

Karen K Brown

Bridget Puffer

Timothy A Mietzner

Charles Issel

Kristina J Hennessy

Feng Li

J Darrell Fontenot

Olivera J Finn

Sarah Burroughs Tencza

Jodi Craigo

Kristina J Hennessey

Michael E Jolley

Mohammad Sarwar Nasir

Sarah B Tencza

Described herein are peptides having antimicrobial activity (antimicrobial peptides). The antimicrobial peptides, designated LBU, WLBU and WR, are analogs of the Lentivirus Lytic Peptide 1 (LLP1) amino acid sequence. The antimicrobial peptides are monomers or multimers of peptides referred to as the Lytic Base Unit (LBU) peptides, derived from the LLP1 analogs and also having antimicrobial activity. Also described herein are using the peptides in a variety of contexts, including the treatment or prevention of infectious diseases. Methods of killing fungi, such asandspecies, and bacteria, such as, are provided herein. Methods of neutralizing enveloped viruses, such as poxvirus, herpesvirus, rhabdovirus, hepadnavirus, baculovirus, orthomyxovirus, paramyxovirus, retrovirus, togavirus, bunyavirus and flavivirus, including influenza virus and HIV-1 also are provided herein. Solid phase substrates and peptide-cargo complexes comprising the peptides also are provided.

Virus derived antimicrobial peptides

The invention provides an equine infectious anemia (EIA) vaccine that provides immunity to mammals, especially equines, from infection with equine infectious anemia virus (EIAV) and which allows differentiation between vaccinated and non-vaccinated, but exposed, mammals or equines. Preferably said vaccine encompasses at least one mutation in an EIAV which produces a non-functional gene in the vaccine virus that is always expressed in disease-producing wild-type EIA viruses. Additionally, said EIA vaccine virus cannot cause clinical disease in mammals or spread or shed to other mammals including equines.

EIA vaccine and diagnostic

The invention is directed to peptides having antimicrobial activity (antimicrobial peptides). The antimicrobial peptides of the present invention are analogs of the Lentivirus Lytic Peptide 1 (LLP1) amino acid sequence. The invention is further directed to peptides referred to as the Lytic Base Unit (LBU) peptides derived from the LLP1 analogs, also having antimicrobial activity. In addition, the present invention is also directed to methods of using the peptides in a variety of contexts, including the treatment or prevention of infectious diseases. The antimicrobial LLP1 analog peptides and the LBU peptides (collectively eLLPs) may be highly active under high salt conditions and in biologic fluids. In addition, the eLLPs are effective when presented either in soluble form, or when attached to a solid surface. Furthermore, the peptides of the present invention are selectively active against a wide variety of bacterial pathogens and exhibit minimal toxicity to eukaryotic cells in vitro and in vivo.

Disclosed herein is a vaccine which provides immunity to mammals from infection and/or disease caused by a lentivirus, such as equine infectious anemia virus, human immunodeficiency virus (HIV), feline immunodeficiency virus (FIV), bovine immunodeficiency virus (BIV) or simian immunodeficiency virus (SIV) said composition comprising a deletion in a gene that blocks replication of the virus in vivo. Preferably said composition encompasses at least one deletion in a lentivirus which provides protection from exposure to wild-type lentiviruses. It also encompasses a marker vaccine in which a foreign gene is inserted into the gene-deleted region, said inserted gene providing a diagnostic tool for use in vaccinated mammals. The scope of the invention encompasses an EIAV vaccine that allows equines to be safely vaccinated and protected from disease without converting to a seropositive status on the Coggin's Test or any other test wich measures p26.

EIAV p26 deletion vaccine and diagnostic

The invention relates to a method for infecting equines with an equine infectious anemia virus (EIAV) in order to reproduce a natural infection challenge model. More specifically, the invention provides a multiple low dose equine EIA challenge model comprising administering at least 1 median horse infective dose to an equine using an intravenous route of administration. It is preferable that the EIAV be administered on a repeated basis. The multiple low dose EIA challenge model described herein can be used for testing efficacy of vaccines, treatments and diagnostic tests.

Equine infectious anemia challenge model for testing vaccines, diagnostics and treatments

Disclosed herein is a vaccine which provides immunity to mammals from infection and/or disease caused by a lentivirus, such as equine infectious anemia virus, human immunodeficiency virus (HIV), feline immunodeficiency virus (FIV), bovine immunodeficiency virus (BIV) or simian immunodeficiency virus (SIV) said composition comprising a deletion in a gene that blocks replication of the virus in vivo. Preferably said composition encompasses at least one deletion in a lentivirus which provides protection from exposure to wild-type lentiviruses. It also encompasses a marker vaccine in which a foreign gene is inserted into the gene-deleted region, said inserted gene providing a diagnostic tool for use in vaccinated mammals. The scope of the invention encompasses an EIAV vaccine that allows equines to be safely vaccinated and protected from disease without converting to a seropositive status on the Coggin's Test or any other test which measures p26.

A fluorescence polarization assay for Equine Infectious Anemia Virus utilizes a short peptide reagent probe derived from a conserved immunodominant region of gp45. The probe is N-terminally labeled, preferably with 6-carboxyfluorescein, and purified by HPLC, which reacts in a homogenous assay with anti-EIAV antibodies contained in the serum of field infected horses and ponies. The assay has a sensitivity of about 90 percent with a specificity approaching 100 percent.

Fluorescence polarization&mdash;based diagnostic assay for equine infectious anemia virus

The invention is directed to antimicrobial peptides which correspond in sequence to selective amino acid sequences in viral transmembrane proteins. In particular, the proteins are derived from lentiviruses, primarily HIV and SIV. The peptides comprise arginine-rich sequences, which, when modeled for secondary structure, display a high amphipathicity and hydrophobic moment. They are highly inhibitory to microorganisms, while being significantly less active in regard to mammalian cells. As a result, the peptides of the invention may be defined as selective antimicrobial agents. The invention is also directed to antimicrobial peptides which are structural and functional analogs and homologs of the peptides and which exhibit selective inhibitory activity towards microorganisms. The invention is also directed to pharmaceutical compositions comprising the antimicrobial peptides of the invention and to methods for their use in inhibiting microbial growth and treatment of microbial infections.

Antimicrobial peptides

The present invention relates to novel synthetic muc-1 peptides and muc-1-like analogs including at least two 20-amino acid tandem repeats of muc-1, which synthetic muc-1 and muc-1-like peptides are capable of attaining native conformation in the absence of glycosylation. The invention also relates to methods of producing the peptides. The invention further relates to uses of the peptides, such as for vaccines and diagnostic testing.

Synthetic multiple tandem repeat mucin and mucin-like peptides, and uses

The present invention relates to novel synthetic muc-1 peptides and muc-1 analogs comprising at least two 20-amino acid tandem repeats of muc-1, wherein said synthetic muc-1 peptide is capable of attaining native conformation in the absence of glycosylation. The invention also relates methods of producing the peptides. The invention further relates to uses of the peptides, such as for vaccines and diagnostic testing.

The present invention discloses peptide vaccines and associated methods for protection against feline leukemia virus (FeLV). The synthetic peptides of the present invention retain their secondary structural identity, stimulate antibodies reactive to the whole virus and elicit a cellular response in vaccinations. These synthetic peptides are inexpensive to produce, stable and permit easy differentiation of vaccinated versus FeLV-infected cats.

Growing community of inventors

Wexford, PA, United States of America

Ronald C Montelaro