Immunotherapeutic compositions for the treatment of alzheimer's disease
A safe and effective vaccine to prevent, slow, halt or reverse progression of Alzheimer's disease in human patients is disclosed. The vaccine includes Aβ1-42 or an beta amyloid self epitope (e.g. Aβ1-15, or other 7-mer or 15-mer peptide epitopes derived from Aβ1-42) conjugated to an immunogenic carrier (e.g. DT) formulated in a water-in-oil Th2-biased adjuvant/delivery system.
1. An immunotherapeutic composition for the treatment of Alzheimer's disease comprising:
an immunogen comprising a peptide comprising an amino acid sequence of 7-15 consecutive amino acid residues of human amyloid beta 1-15 peptide (SEQ ID NO: 2) conjugated to an immunogenic carrier protein, formulated in a water-in-oil emulsion with an oily adjuvant vehicle comprising squalene, squalane and mannide monooleate, and polyoxyl-40-hydrogenated castor oil, wherein the immunogen is contained within aqueous globules that have a median diameter from about 100 nanometers to about 1 micron;
wherein:
the immunogenic carrier protein is diphtheria toxoid carrier;
the immunogen has a conjugation ratio of moles of peptide per mole of carrier of from about 5:1 to about 30:1;
the oily adjuvant vehicle comprises from about 85% to about 90% squalene and squalene, from about 9% to about 12% mannide monooleate and from about 0.5% to about 0.7% polyoxyl 40-hydrogenated castor oil; and
the peptide comprising the amino acid sequence of human amyloid beta protein is coupled to the immunogenic carrier protein via a spacer.
2. The composition of claim 1 wherein the average aqueous globule diameter is about 300 nanometers.
3. The composition of claim 1 , wherein the water-in-oil emulsion comprises from about 65% to about 75% oily globules containing the immunogen.
4. The composition of claim 1 , wherein the squalene and squalene are in a 50/50 ratio by weight.
5. The composition of claim 4 , wherein the oily adjuvant vehicle is Mercia Adjuvant System (MAS-1).
6. The composition of claim 1 , wherein the spacer is a peptide spacer.
7. The immunotherapeutic composition of claim 1 , wherein the immunogen has a conjugation ratio of moles of peptide per mole of carrier of 7:1.
8. The immunotherapeutic composition of claim 1 , wherein the immunogen has a conjugation ratio of moles of peptide per mole of carrier of 22:1.
9. The immunotherapeutic composition of claim 1 , wherein the immunogen has a conjugation ratio of moles of peptide per mole of carrier of 22:1 within the range of about 5:1 to about 25:1.
10. The immunotherapeutic composition of claim 1 , comprising a plurality of immunogens according to claim 1 , said immunogens having conjugation ratios of moles of peptide per mole of carrier within the range of about 5:1 to about 25:1.
11. A method of treating or reducing amyloid plaque deposition in Alzheimer's disease in a human patient, which comprises administering to the patient the immunotherapeutic composition of claim 1 .