A peptide prime-DNA boost immunization protocol provides significant benefits as a new generation Aβ42 DNA vaccine for Alzheimer disease. Academic Article uri icon

Overview

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.

publication date

  • October 1, 2012

Research

keywords

  • Amyloid beta-Peptides
  • Antibody Formation
  • Peptide Fragments
  • Vaccination
  • Vaccines, DNA

Identity

PubMed Central ID

  • PMC4084825

Scopus Document Identifier

  • 84871687263

Digital Object Identifier (DOI)

  • 10.1016/j.jneuroim.2012.09.008

PubMed ID

  • 23036592

Additional Document Info

volume

  • 254

issue

  • 1-2