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Experimental Human Vaccine Developed for West Nile Virus
Date: Mon, 11 March 2002
Vaccine Developed for West Nile virus
Researchers will begin testing the vaccine in monkeys next month and
hope to begin human trials in late 2002. The new vaccine has been
developed by a team from the US National Institute of Allergy and
Infectious Diseases (NIAID) and the Walter Reed Army Institute of
Research. The hybrid vaccine consists mostly of dengue virus, which
does not target the central nervous system. Therefore, it does not
infect the brain. In laboratory tests, the researchers found that the
WNV genes stimulated a powerful immune response in mice who were
given just one shot of the vaccine. One of the dengue viruses used by
the researchers to construct the genetic backbone of this hybrid
virus had already been proven safe in people.
The research is published in the March 5 issue of the Proceedings of
the National Academy of Sciences [Proc. Natl. Acad. Sci. USA, Vol.
99, Issue 5, 3036-3041, 5 Mar 2002:
--
[The PNAS paper by Alexander G. Pletnev, Robert Putnak, Jim Speicher,
Eric J. Wagar and David W. Vaughn is entitled: West Nile virus/dengue
type 4 virus chimeras that are reduced in neurovirulence and
peripheral virulence without loss of immunogenicity or protective
efficacy.
The authors' abstract reads as follows: A candidate live attenuated
vaccine strain was constructed for West Nile virus (WN), a
neurotropic flavivirus that has recently emerged in the U.S.
Considerable attenuation for mice was achieved by chimerization with
dengue virus type 4 (DEN4). The genes for the structural premembrane
and envelope proteins of DEN4 present in an infectious cDNA clone
were replaced by the corresponding genes of WN strain NY99. Two of 18
cDNA clones of a WN/DEN4 chimera yielded full-length RNA transcripts
that were infectious when transfected into susceptible cells. The 2
infectious clones shared a motif in the transmembrane signal domain
located immediately downstream of the NS2B-NS3 protease cleavage site
that separates the DEN4 capsid protein and the WN premembrane protein
of the chimera. This motif, Asp and Thr at a position 3 and 6 amino
acids downstream of the cleavage site, respectively, was not present
in the 16 non-infectious cDNA clones. The WN/DEN4 chimera was highly
attenuated in mice compared with its WN parent; the chimera was at
least 28 500 times less neurovirulent in suckling mice inoculated
intracerebrally and at least 10 000 times less virulent in adult mice
inoculated intraperitoneally. Nonetheless, the WN/DEN4 chimera and a
deletion mutant derived from it were immunogenic and provided
complete protection against lethal WN challenge. These observations
provide the basis for pursuing the development of a live attenuated
WN vaccine. - Mod.CP]
--- end forwarded text
Posted by: Environmental Risk Analysis Program (envrisk@cornell.edu)
-------------------------------------
Scientists have developed [an experimental] vaccine for the deadly
West Nile virus (WNV). It is a hybrid vaccine made up of a
combination of weakened forms of the viruses that cause West Nile
fever and dengue fever. The vaccine is formed by removing key genes
from dengue virus and replacing them with WNV genes.
(http://www.pnas.org/cgi/content/short/99/5/3036)].
ProMED-mail
(promed@promedmail.org)
[see also:
West Nile virus, goose vaccine 20020206.3493
2001
----
West Nile virus, equine vaccine 20010804.1533
West Nile virus, equine vaccine (02) 20010808.1867
West Nile virus, vaccine research 20010607.1117]
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