title: A peptide prime-DNA boost immunization protocol provides significant benefits as a new generation Aβ42 DNA vaccine for Alzheimer disease.
abstract: Immunotherapy has the potential to provide a possible treatment therapy to prevent or delay Alzheimer disease. In a clinical trial (AN1792) in which patients received this immunotherapy and received active Aβ1-42 peptide immunizations, treatment was stopped when 6% of patients showed signs of meningoencephalitis. Follow up on these patients led to the conclusion that the antibody response was beneficial in removing Aβ1-42 from brain but an accompanying inflammatory Th1 T cell response was harmful. As a safe alternative treatment targeting the same self protein, Aβ1-42, in brain, we and others are working on a DNA Aβ1-42 immunization protocol as the immune response to DNA immunizations differs in many aspects from immunizations with peptide antigens. Because the immune response to DNA vaccination has different kinetics and has a significantly lower antibody production, we evaluated two different prime boost regimens, Aβ1-42 DNA prime/Aβ1-42 peptide boost and Aβ1-42 peptide prime/Aβ1-42 DNA boost for their effectiveness in antibody production and possible side effects due to inflammatory T cell responses. While both boost regimes significantly enhanced the specific antibody production with comparable antibody concentrations, the absence of the Aβ1-42 T cell response (no proliferation and no cytokine production) is consistent with our previous findings using this DNA Aβ1-42 trimer immunization and greatly enhances the safety aspect for possible clinical use.
authors.affiliation: Department of Neurology and Neurotherapeutics, University of Texas Southwestern Medical Center, Dallas, TX, United States. Doris.Lambracht-Washington@utsouthwestern.edu
authors.forename: Doris
authors.initials: D
authors.lastname: Lambracht-Washington
authors.forename: Bao-xi
authors.initials: BX
authors.lastname: Qu
authors.forename: Min
authors.initials: M
authors.lastname: Fu
authors.forename: Larry D
authors.initials: LD
authors.lastname: Anderson
authors.forename: Todd N
authors.initials: TN
authors.lastname: Eagar
authors.forename: Olaf
authors.initials: O
authors.lastname: Stüve
authors.forename: Roger N
authors.initials: RN
authors.lastname: Rosenberg
mesh_terms: D016229:Amyloid beta-Peptides / Q000235:genetics* / Q000276:immunology*; D000818:Animals; D000906:Antibodies / Q000097:blood / Q000378:metabolism; D000917:Antibody Formation / Q000276:immunology*; D049109:Cell Proliferation / Q000187:drug effects; D016207:Cytokines / Q000378:metabolism; D004797:Enzyme-Linked Immunosorbent Assay; D018604:Epitope Mapping; D006801:Humans; D051379:Mice; D008815:Mice, Inbred Strains; D010446:Peptide Fragments / Q000008:administration & dosage / Q000235:genetics* / Q000276:immunology*; D013154:Spleen / Q000166:cytology / Q000276:immunology; D013601:T-Lymphocytes / Q000145:classification / Q000187:drug effects / Q000276:immunology; D018418:Th2 Cells / Q000187:drug effects / Q000276:immunology / Q000378:metabolism; D014611:Vaccination / Q000379:methods*; D019444:Vaccines, DNA / Q000276:immunology*
chemical_list: D016229:Amyloid beta-Peptides; D000906:Antibodies; D016207:Cytokines; D010446:Peptide Fragments; D019444:Vaccines, DNA; C075222:amyloid beta-protein (1-42)