Peptide-based immunization therapy for treatment of atherosclerosis

Abstract

The present invention relates to a fragment of apolipoprotein B, for immunization for prophylactic or therapeutic treatment of mammals, including humans, against ischemic cardiovascular diseases, in particular myocardial infarction or stroke, as well as diagnosing the presence or absence of antibodies related to increased or decreased risk of developing ischemic cardiovascular diseases including stroke, using said peptide in an assay, pharmaceutical compositions comprising the peptide. The invention further encompasses a particular peptide sequence aggravating disease, which sequence then can be used for diagnostic assays.

Description

PRIORITY INFORMATION [0001] The present invention is a divisional of U.S. patent application Ser. No. 11 / 373,682 filed on Mar. 10, 2006 which is a continuation of PCT Application No. PCT / SE2004 / 001239, filed on Aug. 30, 2004, which claims priority to Swedish Application No. 0302422-1, filed on Sep. 11, 2003.BACKGROUND OF THE INVENTION [0002] 1.Field of the Invention [0003] The present invention relates to a new peptide, in particular a peptide to be used for immunization therapy for treatment of atherosclerosis, and for development of peptide based immunochemical assay for the determination of immune response against oxidized low density lipoprotein and the diagnosis of the presence or absence of atherosclerosis. [0004] In particular the invention includes: [0005] 1) The use of the peptide of the invention alone, native or MDA-modified, preferably together with a suitable carrier and adjuvant as an immunotherapy or “anti-atherosclerosis “vaccine” for prevention and treatment of isch...

AI Technical Summary

Benefits of technology

[0019] Published studies (Palinski et al., 1995, George et al., 1998 and Zhon et al., 2001) have shown that immunisation against oxidised LDL reduces the development of atherosclerosis. This would suggest that immuno reactions against oxidised LDL in general have a protecting effect. Previous results have (PCT / SE02 / 00679, above), however, surprisingly shown that this is not always the case. Thus in said reference it is shown that using a mixture of peptides #10, 45, 154, 199, and 240 will give rise to an increase of the development of atherosclerosis. Immunisation using other peptide sequences of said reference, e.g., peptide sequences #1, and 30 to 34 lacks total effect on the development of atherosclerosis. The results are surprising because they provide a basis for the fact that immune reactions against oxidised LDL, can protect against the development, contribute to the development of atherosclerosis, and be without any effect at all, depending on which structures in oxidised LDL they are directed to. These findings make it possible to develop immunisation methods, which isolate the activation of protecting immune reactions. Further, they show that immunisation using intact oxidised LDL could have a detrimental effect if the particles used contain a large amount of structures that give rise to atherogenic immuno reactions.

[0024] Oxidation of lipoproteins, mainly LDL, in the arterial wall is believed to be an important factor in the development of atherosclerosis. Products generated during oxidation of LDL are toxic to vascular cells, cause inflammation and initiate plaque formation. Epitopes in oxidized LDL are recognized by the immune system and give rise to T cell activation and antibody formation. A bioinformatics approach has been used to identify a peptide derived from LDL, which can elicit a strong cellular immune response. Animal experiments have shown that this peptide, when derivatized with malondialdehyde (MDA) and used for immunization has a protective effect against atherosclerosis.

Problems solved by technology

Previous results have (PCT / SE02 / 00679, above), however, surprisingly shown that this is not always the case.

Further, they show that immunisation using intact oxidised LDL could have a detrimental effect if the particles used contain a large amount of structures that give rise to atherogenic immuno reactions.

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