DNA epitope vaccine containing complement component C3d enhances anti-amyloid-beta antibody production and polarizes the immune response towards a Th2 phenotype.
We have engineered a DNA epitope vaccine that expresses 3 self-B cell epitopes of Abeta(42) (3Abeta(1-11)), a non-self T helper (Th) cell epitope (PADRE), and 3 copies of C3d (3C3d), a component of complement as a molecular adjuvant, designed to safely reduce CNS Abeta. Immunization of mice with 3Abeta(1-11)-PADRE epitope vaccine alone generated only moderate levels of anti-Abeta antibodies and a pro-inflammatory T helper (Th1 phenotype) cellular immune response. However, the addition of 3C3d to the vaccine construct significantly augmented the anti-Abeta humoral immune response and, importantly, shifted the cellular immune response towards the potentially safer anti-inflammatory Th2 phenotype.
Movsesyan
Nina
N
Department of Molecular Immunology, Institute for Molecular Medicine, Huntington Beach, CA 92647, United States.
Mkrtichyan
Mikayel
M
Petrushina
Irina
I
Ross
Ted M
TM
Cribbs
David H
DH
Agadjanyan
Michael G
MG
Ghochikyan
Anahit
A
D016229:Amyloid beta-Peptides / Q000276:immunology*; D000704:Analysis of Variance; D000818:Animals; D016466:CHO Cells; D015933:Complement C3d / Q000235:genetics / Q000276:immunology*; D006224:Cricetinae; D003412:Cricetulus; D016207:Cytokines / Q000378:metabolism; D004306:Dose-Response Relationship, Immunologic; D004797:Enzyme-Linked Immunosorbent Assay / Q000379:methods; D000939:Epitopes / Q000235:genetics / Q000276:immunology*; D005260:Female; D007074:Immunoglobulin G / Q000145:classification / Q000378:metabolism*; D051379:Mice; D008810:Mice, Inbred C57BL; D010446:Peptide Fragments / Q000276:immunology*; D006377:T-Lymphocytes, Helper-Inducer / Q000276:immunology*; D014162:Transfection; D019444:Vaccines, DNA / Q000235:genetics / Q000276:immunology*
D016229:Amyloid beta-Peptides; D016207:Cytokines; D000939:Epitopes; D007074:Immunoglobulin G; D010446:Peptide Fragments; D019444:Vaccines, DNA; C115195:amyloid beta-protein (1-11); D015933:Complement C3d