Yeast expressed foldable quadrivalent Aβ15 elicited strong immune response against Aβ without Aβ-specific T cell response in wild C57BL/6 mice.

Abstract

Active and passive immunizations with Aβ and Aβ antibodies successfully reduced AD pathology and improved cognitive functions in an AD mouse model. However, human clinical trials of vaccination with synthetic Aβ(AN1792), were halted due to brain inflammation, presumably induced by T cell-mediated immune response. In this study, we used Picha pastoris to produce a recombinant peptide vaccine, r4 × Aβ15(recombinant 4 × Aβ15), four tandem repeats of Aβ(1-15) interlinked by spacers . Wild-type mice were injected subcutaneously with CFA/IFA as adjuvant. r4 × Aβ15 vaccine elicited high titer anti-Aβ antibodies which bound to Aβ plaque in brain tissue from Tg2576 mouse. The antibody isotype was mainly IgG(1), indicating anti-inflammatory Th2 type. There was no splenocyte proliferation against Aβ peptide, which indicates that the r4 × Aβ15 vaccine does not induce Aβ-specific T cellular immune response. Thus, r4 × Aβ15 vaccine may be a safe and efficient vaccine for AD.

• Authors: Lin Tan, Hao Wang, Xin Tan, Juntao Zou, Zhibin Yao
• Journal: Human vaccines & immunotherapeutics (Hum Vaccin Immunother) Vol. 8 Issue 8 Pg. 1090-8 (Aug 2012) ISSN: 2164-554X [Electronic] United States
• PMID: 22854673 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Amyloid beta-Peptides
• Peptide Fragments
• Recombinant Proteins
• Vaccines, Subunit
• amyloid beta-protein (1-15)

Topics

• Alzheimer Disease (immunology, pathology)
• Amyloid beta-Peptides (genetics, immunology, metabolism)
• Animals
• Brain (immunology, pathology)
• Disease Models, Animal
• Injections, Subcutaneous
• Mice
• Mice, Inbred C57BL
• Peptide Fragments (genetics, immunology, metabolism)
• Pichia
• Protein Folding
• Recombinant Proteins (genetics, immunology, metabolism)
• Repetitive Sequences, Amino Acid (genetics, immunology)
• T-Lymphocytes (immunology)
• Vaccines, Subunit (administration & dosage, genetics, immunology, metabolism)