This is the expectationThursday, October 22, 2009
Delivering a Virus Imposter Quicker
With H1N1 vaccine supplies delayed, attention turns to faster-to-make "virus-like
particles."
By David Dobbs
As the current race between H1N1 and vaccine deliveries makes painfully clear, it's
hard to produce a flu vaccine fast enough to outrun a pandemic. But, with two new flu
vaccine candidates beginning clinical trials this month, the "virus-like particle," or
VLP, vaccine may be about to fulfill a long-heralded potential as a flu vaccine that
arrives more quickly.
The key biomedical distinction of a VLP vaccine is its antigen--the component that
provokes an immune response in the person vaccinated. VLP vaccines don't use dead
or weakened flu viruses as antigens, as conventional approaches do. Instead, VLP
vaccines use little protein shells, grown in either plants or insect cells, that look just
like real viruses to the body's immune system but that contain no influenza genetic
material.
"The particle exactly replicates the virus, but because there's none of the genetic
material that makes a virus active, it presents no danger," says Polly Roy, a professor
of virology at the UK's London School of Hygiene and Tropical Medicine who was
one of the first VLP researchers. The lack of genetic material also spares the need for
the formalin and detergent treatments that conventional antigens undergo to render
them noninfectious but that also compromise their power.
Most significant, VLP vaccines can be made quickly. "From the time you identify an
outbreak and publish the genetic sequence online, you can have a vaccine in full
production within three or four months," says Ted Ross, a microbiologist and
geneticist who researches VLPs at the University of Pittsburgh's Center for Vaccine
Research. This offers a huge improvement over the present approach, which has
struggled to produce a vaccine for H1N1 in seven months. It's also fast enough to
check a flu pandemic before it switches hemispheres--as the swine flu did when it
followed the winter from the north to the south this past May and June.
VLPs have been an around-the-corner promise for over 20 years. But they've now
reached a stage at which even disinterested observers believe, as Columbia University
virologist Vincent Racaniello put it, that VLP vaccines "really seem to be coming into
their own." Over the past decade, researchers solved many small but crucial technical
and manufacturing problems, ranging from how to design effective antigens to how to
produce them reliably in quantity. A crucial step came in 2006 when the U.S. Food and
Drug Administration approved the first VLP-based vaccine, Gardasil, the first vaccine
proven effective against the human papillomavirus, which can cause genital warts and
cervical cancer. This was "a huge breakthrough," says the University of Pittsburgh's
Ross, because it suggested that the FDA, generally conservative about vaccines, was
convinced of the safety of VLP-based vaccines.
Since then, VLP flu vaccines have moved onto the fast track, and VLP vaccines have
done well in animal trials against avian, swine, and seasonal flu, and against Ebola as
well. Now two of the leading developers, Novavax, of Maryland, and Medicago, of
Quebec City, have taken VLP flu vaccines all the way through preclinical animal
testing and into human clinical trials, two of which are beginning this month.
The companies use different manufacturing processes. Medicago grows its VLPs in
transgenic tobacco plants, which are simple to manipulate, fast to grow, and easily
raised in high-tech greenhouses that can be built almost anywhere. The company
injects full-grown tobacco plants with genetic information from a target virus, and the
plants produce VLPs in their biomass that can be extracted a few weeks later. Novavax
uses an insect cell-culture approach, growing its VLPs in a line of identical
"immortalized" cells taken 20 years ago from a caterpillar called a fall armyworm. The
armyworm cells are injected with a recombinant baculovirus--a virus that only infects
insects--that is tweaked to resemble a targeted flu virus. The cell responds by
producing and secreting VLPs that have a shell identical to that of the flu virus but
contain no flu RNA.
Both processes are relatively cheap and fast. To illustrate, the 400-person phase I
clinical trial of Novavax's swine flu vaccine candidate that began in Mexico this week
was developed from the genetic information released on the H1N1 virus in early May
and has already been through the design, small-scale production, and animal testing
phases. Over this same time span, conventional makers have just barely started making
the first deliveries of a vaccine that required no fresh design, no animal testing, and
only minimal human testing.
The VLP effort, of course, may trip on any number of obstacles. Yet unless this trial by
Novavax and a parallel avian-flu trial by Medicago reveal a fundamental flaw in the
VLP approach--in contradiction of the successful animal trials of these vaccines and a
successful phase I human trial of Novavax's seasonal flu vaccine--VLP vaccines seem
within reach of becoming the sort of effective, safe, and quickly produced flu vaccine
the world lacks.
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