[pct-l] NYTimes.com Article: Looking for a Vaccine to Defang theLyme Tick

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Looking for a Vaccine to Defang the Lyme Tick

May 20, 2003
By JAMES GORMAN 




 

Dr. José Ribeiro is sequencing the "spitome" of the deer
tick. This is a little bit like sequencing a genome, except
that it has to do with saliva, specifically the saliva of
the deer tick, the tiny menace that lives off deer and
white-footed mice and likes to give suburban gardeners Lyme
disease. 

What Dr. Ribeiro and other scientists at the National
Institute of Allergy and Infectious Diseases in Bethesda,
Md., are finding is that tick spit is a complex weapon,
with an array of components that alleviate pain, keep blood
from coagulating and subdue the host's immune system at the
site of the bite. "Tick saliva is amazing," said Dr. Fred
S. Kantor of the Yale School of Medicine, who is also
working on deciphering tick saliva. 

The goal of the research is to develop a vaccine, not
against the bacteria that causes Lyme, a twisty spirochete
called Borrelia burgdorferi, but against the tick itself. 

More than 16,000 people become infected with the Lyme
disease spirochete each year, and the season starts now,
when nymphs that have been inactive over the winter join
adult ticks in the hunt for blood. Increasing numbers of
ticks are met by increasing numbers of people outside, and
infection rates begin to rise in late spring and summer.
The disease is rarely fatal, but can cause neurological
problems if not treated promptly. Lyme disease is here to
stay, experts say, but anything that can reduce tick
numbers or fight infection would save thousands of people
from a potentially damaging illness. 

In one sense the vaccine research is in the vanguard, since
it is exposing the working of a chemical arsenal that is
not well understood. In another sense, it is a rear-guard
action, a purely defensive maneuver against a prolific and
superbly efficient enemy. A vaccine could not take the
battle to the ticks. It would take effect only when a tick
began drilling for blood. 

Other researchers are working on low-tech tick control
solutions like feeding stations for deer and baited boxes
for mice that are set up to treat the animals' fur with a
pesticide that will kill the ticks. These efforts have met
with some success. 

Both avenues of research are necessary, said Dr. Durland
Fish of the Vector Ecology Laboratory at Yale. But, he
said, he sees a damaging lack of money and energy going
toward tick control and research. Even more of a problem,
he said, is that medical and ecological work are separate.
There is an "artificial division between environmental
science and medicine," he said. "These problems are
identified as medical problems but they require
environmental solutions." 

The vaccine research is squarely in the medical camp. It
was inspired by the observation, as early as 1939, said Dr.
Kantor, whose specialty is immunology, that some animals
develop an immunity to ticks after successive bites. 

Strong immunity has been demonstrated in rabbits, guinea
pigs and humans, he said - but not in white-footed mice,
which are necessary for the life cycle of the Lyme
bacterium. 

He has induced immunity in guinea pigs, he said. "We made
them tick immune by repeated exposure to noninfected
ticks," Dr. Kantor said. When they were exposed to infected
ticks, the creatures fell off sooner, didn't eat as much,
and didn't reproduce as well. 

And, he said, the immunity "profoundly affects
transmission" of Lyme bacteria, although the mechanism is
not clear. The immunity may, he said, stop the bacteria
from leaving the tick at all. 

Unfortunately, subjecting humans to many bites from
uninfected ticks to create immunity is neither appealing
nor practical. Thus, the pursuit of a vaccine. The idea is
to find which genes are active in tick saliva, make copies
of these genes, and insert them in other organisms, and use
those copies to produce more of the proteins the ticks use.


The work has made Dr. Kantor something of an admirer of
ticks. "This little animal," he said, "has an incredible
spectrum in its genome of changing anticoagulants. We found
a whole family of anticoagulants, a whole family." The
chemicals are used by the ticks to keep the blood flowing
as they are feeding. 

The biochemical salvos of saliva are not limited to
anticoagulants. Other components allay pain, so that the
host doesn't notice the drilling, and subdue various kinds
of immune system defenses against the molecules in tick
saliva. The saliva also contains vasodilators to keep veins
and capillaries wide open. 

Dr. Ribeiro and his colleagues in Bethesda are working to
document the whole range of molecules the tick uses in its
saliva. He is sequencing the sialome, or in the common term
that he favors, the spitome. So far, he has found about 90
genes that contain information to produce various
components of the saliva. And he is continuing to search. 

The intriguing aspect of a vaccine against a tick, or any
other vector, or carrier, of disease, he said, is that it
does not need to be as narrowly aimed as a vaccine that
creates an immune response to a specific disease-causing
organism. A vector vaccine would simply stir up such a
storm of immune response, including both defensive
molecules, or antibodies, and killer cells, that the bite
site would be inhospitable to pathogens. 

"Instead of getting into a house where everybody is
sleeping," he said, "you get into a house where everybody
is shooting and you get caught in the crossfire." 

The idea has been shown to be workable. In one published
report, Dr. Jesus Valenzuela, a colleague of Dr. Ribeiro at
the institute, described the creation of a vaccine that
produces an immune reaction to sand fly saliva. Sand flies
carry the parasite that causes a disease called
leishmaniasis. Dr. Valenzuela used cloned genes to recreate
a protein in sand fly saliva and use that in a vaccine. A
result was that vaccinated mice resisted infection by the
parasite when they were bitten by infected flies. 

Sand fly saliva is not as complex as that of ticks, and
unlike ticks, sand flies do not stay on the animals they
bite for very long. But the principle of the vaccine is
similar. Vaccines that respond to tick saliva would have
great value because they could work against more than one
disease. Deer ticks can infect humans with other diseases,
in addition to Lyme, like babesiosis and human granulocytic
ehrlichiosis. Victims may become infected with more than
one, sometimes with all three. 

Another scientist working on tick saliva is Dr. Stephen K.
Wikel at the University of Connecticut Health Center in
Farmington. He said the molecules in tick saliva, in
addition to serving the tick, helped the disease-causing
bacteria. "It's abundantly clear," said Dr. Wikel, "that
these molecules in the spit are essential for successful
pathogen transmission." 

Dr. Wikel and his colleagues are concentrating on the early
period of tick attachment. Deer ticks don't start to draw
blood until several days after they attach. During that
time they prepare the bite site, like oil prospectors
preparing a well for pumping out crude oil. "There are a
lot of different proteins produced early on that are not
produced later on," Dr. Wikel said. 

At the University of Rhode Island, Dr. Thomas N. Mather,
the director of the Center for Vector-Borne Disease in
Kingston, is also looking at what is in the saliva when the
tick is first attached. Saliva is hard to collect then, so
he removes the salivary glands from a creature that is, as
an adult, the size of a sesame seed. "It's always made my
mother proud that I could take out salivary glands from
ticks," he said. Dr. Mather collaborates with Dr. Ribeiro. 

While the research on vaccines looks to the future, and
would result in a defense that begins at the skin, a number
of ways are being devised to control tick populations
before they get to humans. 

One method that has been shown effective is a feeding
station for deer equipped with rollers that apply a
pesticide to the deer fur. 

Dr. Fish at Yale said his tests of this system had shown
reductions in tick populations of 65 percent. He had been
hoping for a greater reductions, but since Lyme infection
rates are directly connected to tick density, that drop is
significant, he said. 

Other methods of tick control are directed at white-footed
mice. Cardboard Damminix tubes have been available for
years. They contain cotton impregnated with permethrin, an
effective tick killer. The idea is that mice collect the
cotton for their nests, and it kills the ticks. 

Dr. Kirby C. Stafford III of the Connecticut Agricultural
Experiment Station in New Haven has been testing bait boxes
designed to attract mice. As the mice go into the box, a
tick killer called Fipronil is brushed on their fur. 

Laboratory prototypes, Dr. Stafford said, were very
effective in reducing tick populations on Mason's Island in
Mystic, Conn., reducing the tick population by 96 percent
after two years. But, he said, that was a small community,
and the prototype boxes required frequent visits to
replenish the pesticide. A commercial product, called
Maxforce, is being tested. 

Research may, however, not be the most important avenue if
simple reduction of Lyme disease cases is the goal. There
are standard recommendations for personal protection that
can help if people are wary. 

Dr. Mather of the University of Rhode Island says he is
convinced that the tools to reduce disease rates are there,
but that awareness is lacking. In areas of very high Lyme
disease rates, where in a few minutes people can collect
500 ticks in a back yard, there is still very little action
and knowledge about what to do, he said. 

People need to receive information at the moment they need
it, he added. 

With a small grant, Dr. Mather said, he planned to start
working on a way to take surveillance data and deliver it
to the public. 

Ideally, he said, he would like to see something like a
tick forecast, the equivalent of weather reports or air
quality or allergy indexes. Then, people would know how to
prepare for a picnic. If tick numbers were down, they might
relax more. If the numbers were up, then people would be
more careful about putting repellents on their clothes. 

For the moment, he said, people cannot go wrong pulling
their socks up over their pants. It is, he said, "the most
cost-effective thing they can do."

http://www.nytimes.com/2003/05/20/science/20TICK.html?ex=1054455652&ei=1&en=6bc1689b4ef9e8fe


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