University of Cape Town

Csir

University of Rochester

South African Medical Research Council

Era Biotech, S.a.

Onderstepoort Biological Products Soc Ltd

Onderstepoort Bilogical Products Soc Ltd

Mitsubishi Tanabe Pharma Corporation

Medicago Inc.

Edward Peter Rybicki

Ann Elizabeth Meyers

Inga Isabel Hitzeroth

Anna-Lise Williamson

Hester Catharina Stark

Emmanuel Aubrey Margolin

James Malcolm Maclean

Martha Magaretha O'Kennedy

Inga Isabel Becker-Hitzeroth

Arvind Devshi Varsani

Nobalanda Betty Mokoena

Daria Anna Rutkowska

Albertha René Van Zyl

Marc-Andre D'Aoust

Pierre-Olivier Lavoie

Robert C Rose

Nathalie Landry

Pablo Marzábal Luna

Peter Öhlschläger

Naomi Asahara

Rosamund Chapman

Masaaki Arai

Fiona Lesley Tanzer

François Devesa

David Levi Rutendo Mutepfa

Livio Heath

This invention relates to a second generation, plant-produced synthetic Orbivirus candidate vaccine. The vaccine comprises a plant produced chimaeric Orbivirus virus like particle (VLP) comprising at least one structural protein from one Orbivirus serotype and at least one structural protein selected from another serotype of the Orbivirus, wherein both structural capsid proteins are from the same Orbivirus species. In particular the invention relates to a vaccine against an Orbivirus, a method of producing chimaeric Orbivirus virus-like particles (VLPs) for use in a method of prevention and/or treatment of an Orbivirus infection, the use of the chimaeric Orbivirus VLPs in the manufacture of a vaccine for an Orbivirus, and a method of preventing and/or treating an Orbivirus infection.

Plant-produced chimaeric orbivirus VLPs

The present invention relates to a fusion protein consisting of a scFv linked to a horseradish peroxidase enzyme or to an alkaline phosphatase enzyme by a peptide linker. The fusion protein also includes a histidine tag and optionally an endoplasmic reticulum retention signal. The invention also includes nucleic acids encoding the fusion protein, expression vectors containing the nucleic acids, plant cells transformed with the expression vectors and methods of producing the fusion proteins of the invention.

Production of a horseradish peroxidase-igg fusion protein

The present invention relates to a method for increasing the expression and/or promoting correct folding of a heterologous polypeptide of interest in a plant cell, comprising co-expressing the heterologous polypeptide of interest with a polypeptide encoding a mammalian chaperone protein. The invention also relates to plant cells and plants, which either transiently or stably, co-express the heterologous polypeptide of interest and the chaperone protein.

Co-expression of human chaperone proteins in plants for increased expression of heterologous polypeptides

Plant-produced chimaeric Orbivirus VLPs

The present invention relates to a method for producing a recombinant HIV glycoprotein polypeptide in a plant and to trimeric complexes of the recombinant, plant-produced HIV glycoprotein polypeptide which mimic the native HIV Env complex. The invention also relates to nucleic acids encoding the recombinant polypeptides, expression vectors containing the aforementioned nucleic acids and to pharmaceutical compositions, uses and methods of eliciting an immune response against HIV in a subject using the recombinant polypeptides and trimeric complexes.

Production of soluble HIV envelope trimers in planta

The present invention relates to a method of producing HPV pseudovirions in plant cells, the plant produced pseudovirions per se, a neutralization assay using the plant produced pseudovirions and pharmaceutical compositions comprising the plant produced pseudovirions.

Plant produced human papillomavirus pseudovirion

This invention relates to a chimaeric human papillomavirus (HPV) virus like particle (VLP) having a diameter of about 30 nm. The invention further relates to methods of treatment and/or prophylaxis of HPV infection and/or cervical cancer by administration of the chimaeric HPV VLP of the invention to a subject.

HPV chimaeric particle

An immunogen-specific is adjuvant for a vaccine or inoculum is disclosed. The adjuvant is comprised of particulate recombinant protein body-like assemblies (RPBLAs) that contain a recombinant fusion protein that contains two portions peptide-linked together. A first portion is a protein body-inducing sequence (PBIS) and a second portion is a T-cell stimulating immunogenic polypeptide whose sequence is that of a pathogenic polypeptide sequence present in or induced by a vaccine or inoculum. The adjuvant, when used as an inoculum in a host animal without a prior priming vaccination or inoculation, does not induce production of antibodies or T cell activation to the pathogenic sequence.

Recombinant protein bodies as immunogen-specific adjuvants

The invention relates to a method of producing an influenza virus H5 polypeptide in a plant comprising the steps of cloning an influenza H5 gene or nucleic acid encoding its functional equivalent into a vector adapted to target components present in the plant, infiltrating at least a portion of the plant with the vector or transforming plant tissue with the vector so as to transiently express the influenza virus H5 polypeptide, and/or to create a transgenic plant; and recover the influenza virus H5 polypeptide expressed by the plant. The invention further relates to vectors, transgenic plants or parts thereof and the progeny of such plants used in or which come about as a result of the method.

Expression of proteins in plants

The invention relates to a method of producing a HPV polypeptides and/or an influenza virus H5 polypeptide in a plant comprising the steps of cloning a HPV gene; and/or an influenza virus H5 gene or nucleic acid encoding their functional equivalents into a vector adapted to target components present in the plant, infiltrating at least a portion of the plant with the vector or transforming plant tissue with the vector so as to transiently express the HPV polypeptides and/or an influenza virus H5 polypeptide, and/or to create a transgenic plant; and recovering the HPV polypeptides and/or an influenza virus H5 polypeptide expressed by the plant. The invention further relates to vectors, transgenic plants or parts thereof and the progeny of such plants used in or which come about as a result of the method.

The invention provides a method for enhancing expression of a transgene in a host cell, which includes the steps of inserting a capsid promoter element (Pcap), or a sequence comprising the reverse complement of the capsid promoter element (PcapR), into a mammalian expression cassette upstream (5') of a cytomegalovirus immediate/early enhancer/promoter region (Pcmv); inserting the transgene into the expression cassette downstream (3&#x2032;) of the cytomegalovirus immediate/early enhancer/promoter region; inserting a vector containing the expression cassette into the host organism; and causing expression of the transgene. The capsid promoter element (Pcap) is typically from a circovirus, parvovirus or anellovirus. The transgene is typically expressed at a higher level than when expressed by a vector containing the expression cassette without the transcriptional control element. An expression cassette, vector, DNA vaccine, pharmaceutical composition and method of treatment are also claimed.

Expression system incorporating a capsid promoter sequence as an enhancer

A method for producing a chimaeric human papillomavirus (HPV) L1 polypeptide containing a heterologous peptide, and in particular, a HPV L2 peptide comprising the steps of introducing a DNA sequence coding for the heterologous peptide into a DNA sequence coding for the L1 polypeptide; introducing the DNA sequence including the sequences for the L1 polypeptide and heterologous peptide into a host cell in which the DNA sequence can be expressed; causing expression of the DNA sequence; and recovering the resulting chimaeric L1 polypeptide which includes the heterologous peptide. The invention also describes a vector for use in the method, a host cell containing the vector, and a vaccine including the chimaeric HPV L1 polypeptide produced according to the method.

Chimaeric human papillomavirus 16 L1 virus-like particles and a method for preparing the particles

The invention describes a method for producing a chimaeric human papillomavirus (HPV) L1 polypeptide containing a heterologous peptide, and in particular, a HPV L2 peptide. The method comprises the steps of introducing a DNA sequence coding for the heterologous peptide into a DNA sequence coding for the L1 polypeptide; introducing the DNA sequence including the sequences for the L1 polypeptide and heterologous peptide into a host cell in which the DNA sequence can be expressed; causing expression of the DNA sequence; and recovering the resulting chimaeric L1 polypeptide which includes the heterologous peptide. Typically, the nucleotides encoding the heterologous peptide replace the nucleotides of the L1 polypeptide at the point of insertion. The invention also describes a vector for use in the method, a host cell containing the vector, and a vaccine including the chimaeric HPV L1 polypeptide produced according to the method.

Chimaeric human papillomavirus 16 I1 virus like particles and a method for preparing the particles

The present invention is directed to a method of expressing the papillomavirus capsid protein coding sequence in a cell using an expression system under conditions facilitating expression of the protein in the cell. In another aspect of the invention, it has been discovered that virus-like particle(s) (VLPs), fragment(s), capsomer(s) or portion(s) thereof are formed from the papillomavirus capsid protein. It was further discovered that the virus-like particle(s) comprises antigenic characteristics similar to those of native infectious papillomavirus particles. In one embodiment of the invention, there is provided a method of expressing the L1 major capsid protein of human papillomavirus type-6 (HPV-6) and type-11 (HPV-11) in Sf-9 insect cells using the baculovirus expression system, and the production of type 6 (HPV-6), type-11 (HPV-11), type-16 (HPV-16) and type-18 (HPV-18) virus-like particles. In yet another embodiment, the invention provides a method of vaccinating a mammal for papillomavirus by administering papillomavirus virus-like particles orally to a mammal in an amount sufficient to induce an immune response to the papillomavirus.

Growing community of inventors

Cape Town, South Africa

Edward Peter Rybicki