NEW YORK (Reuters Health) Mar 04 - An attenuated virus vaccine against
West Nile virus (WN) is efficacious and safe when inoculated into mice,
according to a report in the March 5th issue of the Proceedings of the
National Academy of Sciences. Investigators constructed the vaccine by
substituting the gene encoding the West Nile virus premembrane and envelope
glycoprotein structural proteins for the same genes from the mosquito-borne
dengue type 4 virus (DEN4).
Dr. Alexander G. Pletnev, of the National Institute of Allergy and
Infectious Diseases in Bethesda, Maryland, and colleagues also developed a
similar recombinant DNA vaccine that included a 30-nucleotide deletion in the
3' noncoding region. This procedure has previously been shown to render DEN4
safe and immunogenic in humans.
"In suckling mice the WN/DEN4 chimera was more than 28,571 times less
neurovirulent than its WN parent" when injected intracerebrally, the
investigators note. The 3' deletion mutant was similarly less neurovirulent.
Intraperitoneal inoculation of between 10,000 and 100,000 focus-forming units
(FFU) of the chimeras failed to induce fatal encephalitis in mice, while the
LD-50 for West Nile virus itself was 10 FFU.
Vaccination with 1000 FFU of WN/DEN4 induced a titer of >1:1000
neutralizing antibodies; for the 3' deletion mutant chimera, the result was a
1:292 antibody titer. Challenge with high-dose West Nile virus demonstrated
90% to 100% protection.
"Our observations concerning safety, immunogenicity, and protective
efficacy of the chimeric WN/DEN4 vaccine candidates in mice provide a basis
for extending our evaluation of the vaccine candidates to nonhuman primates
and domestic animals, such as horses, which are at high risk," Dr. Pletnev's
team concludes.
There already exists an inactivated West Nile virus vaccine approved for
use in horses. According to Dr. Robert Chanock, also of the NIAID, a live
attenuated virus vaccine provides broader and longer lasting immunity.
"When you consider the direct economic contributions of the horse
industry--estimated at $25 billion annually--you see why a more effective
vaccine, even if just used for horses, is important," Dr. Chanock told Reuters
Health.
It also has potential as a vaccine for elderly individuals, the population
currently most at risk for CNS complications and mortality due to West Nile
virus, he said.
"West Nile virus has spread in a most dramatic way and probably more
extensively than any other members of the flavivirus family," he noted. "The
problem with flaviviruses is that they are unpredictable, often changing range
or preferred host. For example, St. Louis encephalitis, first recognized in
1933, disappeared for more than 10 years, only to reappear in Texas."
It is thus within the realm of possibility that a version of the vaccine
described here will be necessary for younger individuals, Dr. Chanock added.
Proc Natl Acad Sci USA 2002;99:3036-3041.
