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Colorado State Research Indicates Two Tb Vaccines Show Promise
Monday, June 1, 1998
FORT COLLINS--Researchers at Colorado State University
report that two new vaccines show promise in preventing
tuberculosis in animals.
While not currently as effective as the BCG vaccine,
developed in the 1950s and commonly used in Europe, with further
development the new vaccines may offer long-term immunity,
according to a report by a Colorado State team published in the
June issue of the journal Infection and Immunity.
The vaccines have the potential to supplement BCG, believed
to lose effectiveness over a period of time, and unlike BCG do
not produce positive skin tests for TB in vaccinated individuals.
Ian Orme, professor of microbiology at Colorado State and
head of the 10-person team that evaluated the substances, said
the vaccines, one developed at Colorado State and the other by
the Merck Co., use entirely different approaches to fight
tuberculosis.
BCG isn't used in the United States because until recently,
U.S. medical authorities expected TB to be eradicated early in
the next century. Instead, the disease has become the leading
bacterial killer in the world, causing 10 million new cases and 3
million deaths each year.
Since 1992 Orme and his colleagues have not only pursued
their own basic research interests, but with support from a grant
from the National Institutes of Health have operated a TB vaccine
screening program that has examined dozens of experimental
vaccines, including the two reported on this month.
The vaccines described in the Infection and Immunity article
work in a different fashion than BCG, which triggers an immune
response using weakened bovine tuberculosis bacilli.
The Colorado State vaccine, developed over the past several
years by a team led by Orme, uses specific proteins isolated from
the tuberculosis bacterium. When mixed with interleukin-2, a
protein known to boost the immune system, and added to a carrier
called an adjuvant that also helps boost immunity, the vaccine
simulates a TB infection and generates a specific type of
lymphocyte needed to combat TB infections, Orme said.
The Merck Research Laboratories vaccine, meanwhile, uses a
segment of DNA from Mycobacterium tuberculosis that encodes and
produces a specific protein that also is involved in immunity to
TB. This same approach, using a DNA sequence from a bacterium or
virus to stimulate immunity, has produced other promising
vaccines for influenza and Lyme disease, Orme said.
As for the TB vaccines, "both vaccines tested at Colorado
State give long-term survival against virulent infection that
would normally kill animals in a few weeks," Orme said. "Both
also prevent tissue destruction and actual disintegration of lung
tissues seen in people with active TB."
While not at present as effective as BCG in animal models,
Orme thinks either or both vaccines may eventually prove
effective in supplementing BCG. Used principally outside of the
United States, BCG is given to small children, but evidence
suggests immunity wears off.
"Judging from the results of clinical trials in India and
elsewhere, we're pretty certain that by the age of 15 or 16, BCG
isn't working," Orme said. "Accordingly, I think we should be
looking upon these new vaccines as a boosting mechanism and not
merely as a replacement for BCG."
A major breakthrough of both vaccines tested at Colorado
State is that, unlike the BCG vaccine, they don't trigger a
positive reaction to the skin test commonly used to determine if
an individual actually has TB.
"With these vaccines, a skin test is still possible," Orme
said. "Both the Colorado State and Merck formulations do not
induce a skin test reaction if given alone (i.e., without BCG)."
In the United States, virulent, sometimes drug-resistant
strains have developed among the homeless, AIDS sufferers and
prison populations, and the speed and ease of travel makes
tuberculosis a national as well as global problem, Orme said.
The Colorado State researchers conclude in the Infection and
Immunity article that their findings "provide optimism that
development of nonliving vaccines which can generate long-lived
immunity approaching that conferred by the BCG vaccine is a
feasible goal." However, Orme warned, the effort will be long-
term.
"I will be involved in advising clinicians on setting up
these trials, but it will be my children who will finish them,"
he said. "It may take as many as 25 to 50 years to find out how
effective these vaccines are."
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