NEW YORK (Reuters Health) - Scientists have developed a beta-amyloid DNA-containing vaccine for Alzheimer’s disease that induces an antibody response in mice but does not generate a cell-mediated response, according to a report in the December Archives of Neurology.
This is good news, senior author Dr. Stephen A. Johnston and colleagues suggest. It means that such an approach could be useful in reducing the amyloid plaques that characterize Alzheimer’s disease without increasing the risk of an autoimmune, cell-mediated meningoencephalitis, as occurred in a previous clinical trial of a vaccine composed of amyloid-beta peptide.
The research team, based at the University of Texas Southwestern Medical Center at Dallas, used for their vaccine a plasmid that encoded amyloid-beta fused to gold beads. The particles were delivered to both sides of the ears of mice using a helium-driven gene gun ballistic bombardment method.
Immunization with the plasmid induced significant immune responses, with antibody titers ranging from 1:2000 to 1:10,000, Dr. Johnston’s group notes.
An enzyme-linked immunospot assay for interferon-gamma showed no evident cytotoxic T-lymphocyte response. Using histological and immunoassaying of brain tissues, the authors observed no lymphocytic inflammation or prominent macrophage responses.
According to their report, Dr. Johnston and his associates are continuing their study in order to assess behavioral improvement or slowing of cognitive loss in vaccinated mice, along with effects on amyloid burden, glial response, and inflammatory cell response.
Previous problems with meningoencephalitis “strongly suggest that we need extensive animal studies not only to develop methods of amyloid beta immunization but also to better understand the mechanisms of cellular immune response elicited by amyloid-beta immunization,” Dr. Shoji Tsuji, at the University of Tokyo, writes in an accompanying editorial.
The editorialist adds: “The DNA vaccination approach employing the gene-gun delivery is expected to be an excellent model for such studies.”
Source: Arch Neurol 2004;61:1832,1859-1864. [ Google search on this article ]
MeSH Headings:Amyloid: Amyloid beta-ProteinCopyright © 2002 Reuters Limited. All rights reserved. Republication or redistribution of Reuters content, including by framing or similar means, is expressly prohibited without the prior written consent of Reuters. Reuters shall not be liable for any errors or delays in the content, or for any actions taken in reliance thereon. Reuters and the Reuters sphere logo are registered trademarks and trademarks of the Reuters group of companies around the world.
