Drug – bio-affecting and body treating compositions – Antigen – epitope – or other immunospecific immunoeffector – Recombinant virus encoding one or more heterologous proteins...
Patent
1996-06-05
1999-09-28
Ketter, James
Drug, bio-affecting and body treating compositions
Antigen, epitope, or other immunospecific immunoeffector
Recombinant virus encoding one or more heterologous proteins...
4353201, 435419, 435421, 514 2, 536 234, 536 236, A61K 3912, C12N 1564, C12N 500, C07H 2104
Patent
active
059584220
DESCRIPTION:
BRIEF SUMMARY
This invention relates to the use of viruses as carriers (vectors) for the production or presentation of foreign peptides. More particularly, the invention relates to the genetic manipulation of viral nucleic acid by incorporation of foreign nucleic acid sequences which are expressed as peptides in the virus particle (virion). In this specification the term "foreign", as applied to a peptide or to the nucleic acid encoding therefor, signifies peptide or nucleic acid sequences which are not native to the plant virus used as a vector. Such sequences can be alternatively described as exogenous or heterologous sequences. The term "peptide" includes small peptides and polypeptides.
Our patent application WO 92/18618 describes the utilization of plant viruses as vector systems for the expression of foreign nucleotide sequences, ie nucleotide sequences (RNA or DNA) which are not present in plant viruses, as found in Nature, and which in consequence code for peptides not normally found in any naturally occurring plant virus. The invention described therein comprises assembled particles of a plant virus containing a foreign peptide. The plant viruses of the invention are therefore modified forms of the native viruses and for convenience will be referred to as modified viruses.
The foreign peptides which may be incorporated into plant viruses according to our prior application WO92/18618 may be of highly diverse types and are subject only to the limitation that the nature and size of the foreign peptide and the site at which it is placed in or on the virus particle do not interfere with the capacity of the modified virus to assemble when cultured in vitro or in vivo. In broad concept, modified viruses may be formed from any biologically useful peptides (usually polypeptides) the function of which requires a particular conformation for its activity. This may be achieved by association of the peptide with a larger molecule eg to improve its stability or mode of presentation in a particular biological system. Examples of such peptides are peptide hormones; enzymes; growth factors; antigens of protozoal, viral, bacterial, fungal or animal origin; antibodies including anti-idiotypic antibodies; immunoregulators and cytokines, eg interferons and interleukins; receptors; adhesions; and parts of precursors of any of the foregoing types of peptide. The peptide preferably contains more than 5 amino acids.
Among the broad range of bioactive peptide sequences presented on plant virus vectors in accordance with our prior invention special importance attaches to the antigenic peptides which are the basis of vaccines, particularly animal (including human) virus vaccines. It should be noted that in the context of our prior invention vaccines may have prophylactic (ie disease prevention) or therapeutic (ie disease treatment) applications. For vaccine applications our prior invention provides an especially attractive epitope presentation system. When used for such applications the antigenic peptide component will be sited appropriately on the virus particle so as to be easily recognised, by the immune system, for example by location on an exposed part of the coat protein of the virus. As applied to the latter, therefore, our prior invention comprises assembled particles of a modified plant virus containing an antigen derived from a pathogen, eg an animal virus, incorporated in an exposed position on the surface of the coat protein of the plant virus. This invention also comprises the use of such assembled modified plant virus particles as the immunogenic component of a vaccine. Such assembled modified plant virus particles presenting antigenic peptides also have applications as the antigen presentation component of an immunodiagnostic assay for detection of eg animal (including human) pathogens and diseases.
The system described in our prior application is highly versatile in regard to the size of the foreign peptide which may be inserted into the viral coat protein. Thus peptides containing up to 38 or more amino acids have been suc
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Axis Genetics PLC
Ketter James
Sandals William
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