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US 2004/0002111 A1Published application
Atherosclerosis vaccine
OwnerGoran Hansson, Sten Stemme +2inventors
InventorsGoran Hansson, Sten Stemme, Antonio Nicoletti, Dirk Wuttge
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OwnerGoran Hansson, Sten Stemme +2inventors
InventorsGoran Hansson, Sten Stemme, Antonio Nicoletti, Dirk Wuttge
Estimating the term…
The present invention relates to an antigenic composition capable of eliciting antibodies by interacting with αβ chains of a T cell receptor (TcR), which composition is comprised of a peptide-aldehyde conjugate. The aldehyde portion may be a dialdehyde, such as malondialdehyde (MDA), or a monoaldehyde, such as 4-hydroxynonenal (4-HNE), while the peptide portion preferably comprises at least one lysine residue. The antigenic composition according to the invention is capable of recognizing and interacting with a TcR having a complementarity-determining region 3 (CDR3) of α10 and β6 chains that comprises a cluster of charged and polar amino acids. The invention also relates to a method of producing a vaccine against atherosclerosis by screening of a library of candidate compounds for their ability to bind to a conjugate of oxidized LDL and a dialdehyde as well as to such a vaccine as such.
An antigenic composition comprised of a peptide, which is derived from the protein apoB100, conjugated with an aldehyde, and capable of eliciting an immune response against non-native, oxidized low density lipoprotein (LDL) in a subject by interacting with T cell antigen receptors (TrR).
A composition according to any one of the preceding claims, wherein the peptide comprises at least one lysine residue.
A composition according to any one of the preceding claims, wherein the peptide contains amino acid residues that promote the formation of a polyproline-like structure.
A composition according to any one of the preceding claims, the antigenic properties of which is enhanced by association with a major histocompatibility (MHC) class II antigen.
A composition according to any one of the preceding claims, wherein the complementarity-determining region 3 (CDR3) of said TcR comprises a cluster of amino acids the spatial configuration of which enables binding of the peptide-aldehyde conjugate.
A composition according to any one of the preceding claims, wherein said TcR chains are α10 and β6 chains essentially of the sequence disclosed in SEQ ID NO:4 and SEQ ID NO:2, respectively, or an antigenic derivative, fragment or analogue thereof, or a TcR that contains a CDR3 region with high structural or conformational homology to said TcR.
An immunogenic cell, which has been induced to carry MDA-protein conjugates.
A method of generating an MHC class II molecule corresponding to a predetermined haplotype, which method comprises expression of peptide in a suitable expression system and subsequently conjugation of the expression product to an aldeyde, such as MDA or 4-HNE.
Use of a peptide derived from the protein apoB100 conjuated with an aldehyde, which conjugate is capable of eliciting an immune response against non-native, oxidized low density lipoprotein (LDL) in a subject by interacting with T cell antigen receptors (TcR), in the manufacture of a vaccine against atherosclerosis.
A method of producing a vaccine against atherosclerosis, which comprises the steps of
A method of producing a vaccine against atherosclerosis, which comprises the steps of
Use of a T cell receptor (TcR) comprising an amino acid sequence essentially as defined by SEQ ID NO;4 and SEQ ID NO:2, or a functional derivative, fragment or analogue thereof, as a lead compound in a method of molecular modelling of a ligand capable of binding said TcR, said three dimensional structure being characterised by a flattened surface and the presence of exposed surface charges.
Dependencies are inferred from the claim text.