NEW YORK (Reuters Health) - Scientists have identified a mouse monoclonal antibody (E16) that neutralizes 10 different strains of West Nile virus (WNV) in vitro and shows significant therapeutic efficacy in a mouse model of WNV infection.
“The E16 antibody has been cloned and humanized as a first step towards potential human use,” Dr. Michael S. Diamond from Washington University School of Medicine in St. Louis told Reuters Health. This antibody “may be a viable treatment option against WNV infection in humans,” he and colleagues write in the April 24th advance online issue of Nature Medicine.
The E16 antibody targets a single dominant neutralizing epitope on domain III of the WNV E protein. Convalescent antibodies from patients who recovered from WNV infection have also recognized this epitope.
According to investigators, a single dose of the mouse E16 antibody administered 5 days after infection, prevented WNV-induced morbidity and mortality in mice. “This time point is significant because virus enters the brain 4 days after infection in the mice, so these mice effectively had WNV encephalitis at the time of treatment,” Dr. Diamond told Reuters Health.
The mouse E16 antibody was able to clear virus infection in the brain in the majority of mice by day 9 after infection.
The humanized E16 antibody “retained antigen specificity, affinity, neutralizing activity in cells, and protective activity in vivo even when administered several days after infection,” Dr. Diamond reported.
Washington University has licensed the antibody to Rockville, Maryland-based MacroGenics, which will continue independently to pursue its development as a possible therapeutic, Dr. Diamond said.
Meanwhile, his group is working to determine the precise structural and molecular mechanism of how antibodies such as E16 neutralize WNV. “We have also begun studies to determine the analogous epitope in dengue viruses. Hopefully, these studies will also have implications for the development of safe and effective vaccines against these viruses by targeting antibody responses,” he said.
Source: Nature Med 2005. [ Google search on this article ]
MeSH Headings:Animal Diseases: Disease Models, Animal: Drugs, Investigational: DiseasesCopyright © 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.
